B Lymphocytes: Receptors

Abstract

B lymphocytes can synthesise Ig heavy chains that are either secreted or membrane‐bound, the latter having a transmembrane domain and a short cytoplasmic domain. Membrane‐bound Ig heavy chains and Ig light chains assemble in the ER with each other and with a heterodimer of Igα and Igβ, which mediate signalling and internalisation functions. The complex of these four polypeptides is called the B cell antigen receptor (BCR). BCR signalling occurs via three types of tyrosine kinases. Src‐family kinases phosphorylate the two tyrosine‐containing motif in the cytoplasmic domains of Igα and Igβ (the ITAMs), which recruits a second type of tyrosine kinase Syk. Syk is responsible for most downstream signalling, although calcium and diacylglycerol also require a third tyrosine kinase Btk. BCR signalling pathways are central to virtually all aspects of B cell biology, as they are required for B cell development, tolerance induction, survival and activation.

Key Concepts

  • Naïve B cells express their immunoglobulin as a cell surface receptor for antigen, called the BCR (B cell receptor for antigen).
  • In developing precursors of B cells, the successful generation of an immunoglobulin heavy chain is sensed by the incorporation of that heavy chain into pre‐BCR molecules, which exhibit constitutive signalling.
  • Signalling by the BCR controls development, survival and activation of B cells in a manner that is dependent on the developmental stage or activation state of the B cell. This signalling is important both for tolerisation of self‐reactive B cells and for activation of B cells recognising foreign antigen.
  • Co‐receptors that recognise complement components, sialic acid residues, or IgG bound to antigens strongly enhance or inhibit signalling by the BCR to aid in self‐non‐self‐discrimination.
  • The BCR is also an endocytic receptor that delivers antigen to internal compartments where protein antigens are processed into peptides and loaded onto MHC class II molecules to facilitate interactions with T cells, which are essential for production of high‐affinity antibodies.
  • Defects in generation of BCRs or signalling components of the BCR result in B cell immunodeficiencies, the most common of which is due to loss‐of‐function mutations of the intracellular protein tyrosine kinase Btk, referred to as X‐linked agammaglobulinemia.
  • B cell malignancies often have activated BCR signalling as a driver of their proliferation and/or survival, and selective Btk inhibitors are now approved therapeutics for some types of B cell malignancies.

Keywords: antibody; membrane immunoglobulin; BCR; pre‐BCR; protein tyrosine kinase; Syk; Btk; ITAM; phosphoinositide signalling

Figure 1. Structure of the BCR and the pre‐BCR. The BCR and pre‐BCR are analogous structures with the main difference being the presence in the BCR of a κ or λ light chain and the presence in the pre‐BCR of ‘surrogate light chain’, composed of VpreB and λ5. The non‐Ig domain parts of the surrogate light chain (represented by curving lines) provide a function that is required for B cell development, as discussed in the text. Box in the cytoplasmic domain of Igα and Igβ represents the ITAM sequence.
Figure 2. Schematic overview of the antibody response. See the text for details.
Figure 3. Antigen binding to the BCR triggers the following series of events: (1) phosphorylation of BCR ITAM tyrosines by the Src‐family tyrosine kinases (Lyn, Fyn and Blk); (2) binding of Syk to doubly phosphorylated ITAMs via its two SH2 domains (represented by oval indentations); (3) activation of Syk by a combination of binding via its SH2 domains and activating phosphorylations performed by neighbouring protein tyrosine kinases (Src‐family tyrosine kinases or Syk bound to a co‐clustered BCR) and (4) phosphorylation of tyrosines of signalling target molecules primarily by Syk but to some extent by Src family kinases. ‘P’ represents phosphorylated tyrosine residue.
Figure 4. BCR engagement induces the formation of signalling complexes. Two major signalling complexes are formed in response to BCR engagement. Left: SLP65 (also called BLNK) is pre‐associated with Cbl‐interacting protein of 85 kDa (CIN85) via interaction of proline‐rich motifs of SLP65 with the three SH3 domains of CIN85. Upon engagement of the BCR, CIN85 is recruited to the BCR, but the exact mechanism of this recruitment is not well defined. Upon recruitment, Syk phosphorylates multiple tyrosines in the ‐terminal region of SLP65, which in turn recruit PLCγ2, Btk and Vav. Btk becomes activated by phosphorylation and participates in the activation of PLCγ2 by phosphorylating it. Not shown, recruitment of Btk and PLCγ2 to SLP65 is aided by pleckstrin homology (PH) domains of these proteins, which have specificity for PIP3. In addition, the ‐terminal SH2‐domain of SLP65 can bind to a non‐ITAM‐phosphorylated tyrosine of Igα (Y204), but this interaction is not required for SLP65 function, at least under conditions of vigorous signalling. Right: PI 3‐kinase is activated following BCR engagement by two main mechanisms. CD19 has two tyrosines in its cytoplasmic domain that serve as binding sites for the SH2 domain of the regulatory subunit of PI 3‐kinase (p85, shown in blue), which is pre‐bound to the catalytic p110 subunit (shown in orange). This mechanism is especially important if the antigen has complement components deposited on it, as CD19 is in a complex with CR2 (CR2, also called CD21) (Figurea), but it is also important if the antigen is attached to a cell surface. In addition, PI 3‐kinase is recruited to the BCR and activated via a complex between Nck and BCAP, which forms due to the SH3 domains of Nck1 or Nck2 binding to proline‐rich regions of BCAP. The SH2 domain of Nck binds to tyrosine‐phosphorylated Y204 of Igα, which recruits BCAP, leading to its phosphorylation and recruitment to the membrane of PI 3‐kinase. Nck and Vav also both participate in regulation of actin remodelling, which is also an important element of BCR signalling. SLP65 and Nck compete for binding to tyrosine‐phosphorylated Y204 of Igα; current evidence indicates that the Nck interaction is the more important one. Not shown is that BCR engagement also leads to assembly of the CARMA‐1, Bcl‐10, MALT1 complex that activates NF‐κB. SH3 domains in Nck and CIN85 are indicated. SH2 domains of significance are indicated by oval indentations. Other important protein domains such as PH domains are not shown.
Figure 5. Signalling pathways involving phosphoinositol‐containing phospholipids. Shown in red are the key second messengers generated by PLCγ2 and PI 3‐kinase, the two upstream enzymes acting on PIP2. In blue are the key enzymes that are activated by these second messengers, which includes PLCγ2, representing a connection between the two major pathways. Note that protein kinase C (PKC) comes in multiple isoforms and the isoform involved in NF‐κB activation is PKCβ. PKCδ has also been shown to be important for regulating B cell function, but how it is activated and its key targets are not well defined. Inhibitory enzymes are in orange. DG, diacylglycerol and IP3+, inositol 1,4,5‐trisphosphate. See the text for details.
Figure 6. (a): The complement receptor 2 (CR2, also called CD21) complex on B cells is a positive co‐receptor that can greatly enhance B cell activation. The presence of complement fragments (breakdown fragments of C3b, including C3d) attached to the antigen recruit the CR2 complex of B cells, which includes CD19 and the tetraspanin CD81, to the membrane near the BCR. BCR‐associated protein tyrosine kinases such as Syk then phosphorylate the cytoplasmic tail of CD19, which creates binding sites for the p85 regulatory subunit of PI 3‐kinase. PI 3‐kinase is recruited to the membrane where it has access to its substrate PIP2 (see Figure). This mechanism is thought to represent a means of self‐non‐self‐discrimination, as the alternative pathway of complement or low‐affinity IgM can promote C3b deposition on foreign particles or debris, whereas host cells have complement inhibitory proteins on their surface that rapidly destroy any complement components that may be deposited on them. (b): Inhibitory co‐receptors of B cells can inhibit activation of B cells if there are already sufficient levels of circulating IgG recognising the antigen (left) or if the antigen contains terminal sialic acid residues in linkages characteristic of self‐oligosaccharides on glycoproteins or glycolipids (right). FcγRIIb and the Siglec family members CD22 and Siglec G (not shown) are inhibitory receptors with one or more tyrosine‐containing ITIM motifs in their cytoplasmic domains. Once phosphorylated, these motifs recruit either the SH2‐containing inositol phosphatase (SHIP), which removes a phosphate from PIP3 and thereby counters PI 3‐kinase signalling (see Figure), or the SH2‐containing protein tyrosine phosphatase SHP‐1 (also called PTPN6), which counters signalling by Syk and Src‐family tyrosine kinases at proximal steps. Among the Src‐family tyrosine kinases, only Lyn can phosphorylate ITIMs, whereas Lyn, Fyn and Blk are all able to phosphorylate ITAMs and contribute positively to BCR signalling. While this figure emphasises the role of CD22 in inhibiting BCR signalling when the antigen has sialic acid bound to it, CD22 also attenuates BCR signalling in a manner that is controlled by lateral interactions with sialic acid‐containing glycoproteins on the B cell surface (not shown).
close

References

Avalos AM and Ploegh HL (2014) Early BCR events and antigen capture, processing, and loading on MHC class II on B cells. Frontiers in Immunology 5: 00092.

Bankovich AJ, Raunser S, Juo ZS, et al. (2007) Structural insight into pre‐B cell receptor function. Science 316: 291–294.

Bannish G, Fuentes‐Pananá EM, Cambier JC, et al. (2001) Ligand‐independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis. Journal of Experimental Medicine 194: 1583–1596.

Brdicka T, Kadlecek TA, Roose JP, et al. (2005) Intramolecular regulatory switch in ZAP‐70: analogy with receptor tyrosine kinases. Molecular and Cellular Biology 25: 4924–4933.

Browne CD, Del Nagro CJ, Cato MH, et al. (2009) Suppression of phosphatidylinositol 3,4,5‐trisphosphate production is a key determinant of B cell anergy. Immunity 31: 749–760.

Busman‐Sahay K, Drake L, Sitaram A, et al. (2013) Cis and trans regulatory mechanisms control AP2‐mediated B cell receptor endocytosis via select tyrosine‐based motifs. PLoS One 8: e54938.

Cariappa A, Takematsu H, Liu H, et al. (2009) B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9‐O‐acetyl sialic acid esterase. Journal of Experimental Medicine 206: 125–138.

Carter RH and Fearon DT (1992) CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256: 105–107.

Castello A, Gaya M, Tucholski J, et al. (2013) Nck‐mediated recruitment of BCAP to the BCR regulates the PI(3)K‐Akt pathway in B cells. Nature Immunology 14: 966–975.

Chan TD, Gatto D, Wood K, et al. (2009) Antigen affinity controls rapid T‐dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. Journal of Immunology 183: 3139–3149.

Chaturvedi A, Dorward D and Pierce SK (2008) The B cell receptor governs the subcellular location of Toll‐like receptor 9 leading to hyperresponses to DNA‐containing antigens. Immunity 28: 799–809.

Conley ME, Dobbs AK, Farmer DM, et al. (2009) Primary B cell immunodeficiencies: comparisons and contrasts. Annual Review of Immunology 27: 199–227.

Coughlin JJ, Stang SL, Dower NA, et al. (2005) RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor‐Ras signaling. Journal of Immunology 175: 7179–7184.

Crowley MT, Costello PS, Fitzer‐Attas CJ, et al. (1997) A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages. Journal of Experimental Medicine 186: 1027–1039.

Davis RE, Ngo VN, Lenz G, et al. (2010) Chronic active B‐cell‐receptor signalling in diffuse large B‐cell lymphoma. Nature 463: 88–92.

Delgado P, Cubelos B, Calleja E, et al. (2009) Essential function for the GTPase TC21 in homeostatic antigen receptor signaling. Nature Immunology 10: 880–888.

Depoil D, Fleire S, Treanor BL, et al. (2008) CD19 is essential for B cell activation by promoting B cell receptor‐antigen microcluster formation in response to membrane‐bound ligand. Nature Immunology 9: 63–72.

Dykstra M, Cherukuri A, Sohn HW, et al. (2003) Location is everything: lipid rafts and immune cell signaling. Annual Review of Immunology 21: 457–481.

Elantak L, Espeli M, Boned A, et al. (2012) Structural basis for galectin‐1‐dependent pre‐B cell receptor (pre‐BCR) activation. Journal of Biological Chemistry 287: 44703–44713.

Engels N, König LM, Schulze W, et al. (2014) The immunoglobulin tail tyrosine motif upgrades memory‐type BCRs by incorporating a Grb2‐Btk signalling module. Nature Communications 5: 5456.

Espeli M, Mancini SJ, Breton C, et al. (2009) Impaired B‐cell development at the pre‐BII‐cell stage in galectin‐1‐deficient mice due to inefficient pre‐BII/stromal cell interactions. Blood 113: 5878–5886.

Feske S, Wulff H and Skolnik EY (2015) Ion channels in innate and adaptive immunity. Annual Review of Immunology 33: 291–353.

Fitzer‐Attas CJ, Lowry M, Crowley MT, et al. (2000) Fcgamma receptor‐mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn. Journal of Experimental Medicine 191: 669–682.

Fuentes‐Pananá EM, Bannish G, Karnell FG, et al. (2006) Analysis of the individual contributions of Igalpha (CD79a)‐ and Igbeta (CD79b)‐mediated tonic signaling for bone marrow B cell development and peripheral B cell maturation. Journal of Immunology 177: 7913–7922.

Gazumyan A, Reichlin A and Nussenzweig MC (2006) Ig beta tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization. Journal of Experimental Medicine 203: 1785–1794.

Green NM and Marshak‐Rothstein A (2011) Toll‐like receptor driven B cell activation in the induction of systemic autoimmunity. Seminars in Immunology 23: 106–112.

Gross AJ, Lyandres JR, Panigrahi AK, et al. (2009) Developmental acquisition of the Lyn‐CD22‐SHP‐1 inhibitory pathway promotes B cell tolerance. Journal of Immunology 182: 5382–5392.

Gupta N, Wollscheid B, Watts JD, et al. (2006) Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin regulates antigen receptor‐mediated lipid raft dynamics. Nature Immunology 7: 625–633.

Harwood NE and Batista FD (2010) Early events in B cell activation. Annual Review of Immunology 28: 185–210.

Hou B, Saudan P, Ott G, et al. (2011) Selective utilization of Toll‐like receptor and MyD88 signaling in B cells for enhancement of the antiviral germinal center response. Immunity 34: 375–384.

Hou P, Araujo E, Zhao T, et al. (2006) B cell antigen receptor signaling and internalization are mutually exclusive events. PLoS Biology 4: e200.

Hua Z, Gross AJ, Lamagna C, et al. (2014) Requirement for MyD88 signaling in B cells and dendritic cells for germinal center anti‐nuclear antibody production in Lyn‐deficient mice. Journal of Immunology 192: 875–885.

Karnell FG, Brezski RJ, King LB, et al. (2005) Membrane cholesterol content accounts for developmental differences in surface B cell receptor compartmentalization and signaling. Journal of Biological Chemistry 280: 25621–25628.

Kraus M, Pao LI, Reichlin A, et al. (2001) Interference with immunoglobulin (Ig)alpha immunoreceptor tyrosine‐based activation motif (ITAM) phosphorylation modulates or blocks B cell development, depending on the availability of an Igbeta cytoplasmic tail. Journal of Experimental Medicine 194: 455–469.

Kurosaki T and Hikida M (2009) Tyrosine kinases and their substrates in B lymphocytes. Immunology Reviews 228: 132–148.

Kurosaki T, Shinohara H and Baba Y (2010) B Cell Signaling and Fate Decision. Annual Review of Immunology 28: 21–55.

Lam KP, Kühn R and Rajewsky K (1997) In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90: 1073–1083.

Lamagna C, Hu Y, DeFranco AL, et al. (2014) B cell‐specific loss of Lyn kinase leads to autoimmunity. Journal of Immunology 192: 919–928.

Lang P, Stolpa JC, Freiberg BA, et al. (2001) TCR‐induced transmembrane signaling by peptide/MHC class II via associated Ig‐alpha/beta dimers. Science 291: 1537–1540.

Law DA, Chan VW, Datta SK, et al. (1993) B‐cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn. Current Biology 3: 645–657.

Lenz G, Davis RE, Ngo VN, et al. (2008) Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319: 1676–1679.

Limnander A, Zikherman J, Lau T, et al. (2014) Protein kinase Cδ promotes transitional B cell‐negative selection and limits proximal B cell receptor signaling to enforce tolerance. Molecular and Cellular Biology 34: 1474–1485.

Lin KB, Freeman SA, Zabetian S, et al. (2008) The rap GTPases regulate B cell morphology, immune‐synapse formation, and signaling by particulate B cell receptor ligands. Immunity 28: 75–87.

Mattila PK, Feest C, Depoil D, et al. (2013) The actin and tetraspanin networks organize receptor nanoclusters to regulate B cell receptor‐mediated signaling. Immunity 38: 461–474.

Mukherjee S, Zhu J, Zikherman J, et al. (2013) Monovalent and multivalent ligation of the B cell receptor exhibit differential dependence upon Syk and Src family kinases. Science Signaling 6: ra1.

Müller J and Nitschke L (2014) The role of CD22 and Siglec‐G in B‐cell tolerance and autoimmune disease. Nature Reviews. Rheumatology 10: 422–428.

Natkanski E, Lee WY, Mistry B, et al. (2013) B cells use mechanical energy to discriminate antigen affinities. Science 340: 1587–1590.

O'Neill SK, Getahun A, Gauld SB, et al. (2011) Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP‐1 phosphatase‐mediated inhibitory signaling cascade required for B cell anergy. Immunity 35: 746–756.

O'Neill SK, Veselits ML, Zhang M, et al. (2009) Endocytic sequestration of the B cell antigen receptor and toll‐like receptor 9 in anergic cells. Proceedings of the National Academy of Sciences of the United States of America 106: 6262–6267.

Oellerich T, Bremes V, Neumann K, et al. (2011) The B‐cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. EMBO Journal 30: 3620–3634.

Pao LI, Lam KP, Henderson JM, et al. (2007) B cell‐specific deletion of protein‐tyrosine phosphatase Shp1 promotes B‐1a cell development and causes systemic autoimmunity. Immunity 27: 35–48.

Pierce SK and Liu W (2010) The tipping points in the initiation of B cell signalling: how small changes make big differences. Nature Reviews Immunology 10: 767–777.

Pincetic A, Bournazos S, DiLillo DJ, et al. (2014) Type I and type II Fc receptors regulate innate and adaptive immunity. Nature Immunology 15: 707–716.

Radaev S, Zou Z, Tolar P, et al. (2010) Structural and functional studies of Igalphabeta and its assembly with the B cell antigen receptor. Structure 18: 934–943.

Rawlings DJ, Sommer K and Moreno‐Garcia ME (2006) The CARMA1 signalosome links the signalling machinery of adaptive and innate immunity in lymphocytes. Nature Reviews Immunology 6: 799–812.

Rickert RC (2013) New insights into pre‐BCR and BCR signalling with relevance to B cell malignancies. Nature Reviews Immunology 13: 578–591.

Rookhuizen DC and DeFranco AL (2014) Toll‐like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses. Proceedings of the National Academy of Sciences of the United States of America 111: E3224–3233.

Saijo K, Schmedt C, Su I, et al. (2003) Essential role of Src‐family protein tyrosine kinases in NF‐kappaB activation during B cell development. Nature Immunology 4: 274–279.

Sohn HW, Tolar P and Pierce SK (2008) Membrane heterogeneities in the formation of B cell receptor‐Lyn kinase microclusters and the immune synapse. Journal of Cell Biology 182: 367–379.

Srinivasan L, Sasaki Y, Calado DP, et al. (2009) PI3 kinase signals BCR‐dependent mature B cell survival. Cell 139: 573–586.

Stoddart A, Dykstra ML, Brown BK, et al. (2002) Lipid rafts unite signaling cascades with clathrin to regulate BCR internalization. Immunity 17: 451–462.

Surolia I, Pirnie SP, Chellappa V, et al. (2010) Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 466: 243–247.

Tze LE, Schram BR, Lam KP, et al. (2005) Basal immunoglobulin signaling actively maintains developmental stage in immature B cells. PLoS Biology 3: e82.

Übelhart R, Hug E, Bach MP, et al. (2015) Responsiveness of B cells is regulated by the hinge region of IgD. Nature Immunology 16: 534–543.

Vaughn SE, Kottyan LC, Munroe ME, et al. (2012) Genetic susceptibility to lupus: the biological basis of genetic risk found in B cell signaling pathways. Journal of Leukocyte Biology 92: 577–591.

Vilen BJ, Nakamura T and Cambier JC (1999) Antigen‐stimulated dissociation of BCR mIg from Ig‐alpha/Ig‐beta: implications for receptor desensitization. Immunity 10: 239–248.

Wang Y and Carter RH (2005) CD19 regulates B cell maturation, proliferation, and positive selection in the FDC zone of murine splenic germinal centers. Immunity 22: 749–761.

Wheeler ML, Dong MB, Brink R, et al. (2013) Critical role of diacylglycerol kinase zeta in limiting B cell antigen receptor‐induced ERK signaling and controlling the magnitude of the extrafollicular plasmablast. Sci Signaling 6: ra91.

Wienands J and Reth M (1992) Glycosyl‐phosphatidylinositol linkage as a mechanism for cell‐surface expression of immunoglobulin D. Nature 356: 246–248.

Winslow MM, Gallo EM, Neilson JR, et al. (2006) The calcineurin phosphatase complex modulates immunogenic B cell responses. Immunity 24: 141–152.

Xu Y, Xu L, Zhao M, et al. (2014) No receptor stands alone: IgG B‐cell receptor intrinsic and extrinsic mechanisms contribute to antibody memory. Cell Research 24: 651–664.

Yang J and Reth M (2010) Oligomeric organization of the B‐cell antigen receptor on resting cells. Nature 467: 465–469.

Young RM, Shaffer AL, Phelan JD, et al. (2015) B‐cell receptor signaling in diffuse large B‐cell lymphoma. Seminars in Hematology 52: 77–85.

Ysebaert L and Michallet AS (2014) Bruton's tyrosine kinase inhibitors: lessons learned from bench‐to‐bedside (first) studies. Current Opinion in Oncology 26: 463–468.

Zhang M, Veselits M, O'Neill S, et al. (2007) Ubiquitinylation of Ig beta dictates the endocytic fate of the B cell antigen receptor. Journal of Immunology 179: 4435–4443.

Zhu JW, Brdicka T, Katsumoto TR, et al. (2008) Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling. Immunity 28: 183–196.

Zidovetzki R, Rost B and Pecht I (1998) Role of transmembrane domains in the functions of B‐ and T‐cell receptors. Immunology Letters 64: 97–107.

Zikherman J, Parameswaran R and Weiss A (2012) Endogenous antigen tunes the responsiveness of naive B cells but not T cells. Nature 489: 160–164.

Further Reading

Baba Y, Matsumoto M and Kurosaki T (2014) Calcium signaling in B cells: regulation of cytosolic Ca2+ increase and its sensor molecules STIM1 and STIM2. Molecular Immunology 62: 339–343.

Goodnow CC, Vinuesa CG, Randall KL, et al. (2010) Control systems and decision making for antibody production. Nature Immunology 11: 681–688.

Harwood NE and Batista FD (2008) New insights into the early molecular events underlying B cell activation. Immunity 28: 609–619.

Kometani K and Kurosaki T (2015) Differentiation and maintenance of long‐lived plasma cells. Current Opinion in Immunology 33: 64–69.

Pereira JP, Kelly LM and Cyster JG (2010) Finding the right niche: B‐cell migration in the early phases of T‐dependent antibody responses. International Immunology 22: 413–419.

Victora GD and Nussenzweig MC (2012) Germinal centers. Annual Review of Immunology 30: 429–457.

Viola A and Gupta N (2007) Tether and trip: regulation of membrane‐raft dynamics by actin‐binding proteins. Nature Reviews Immunology 7: 889–896.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
DeFranco, Anthony L(Nov 2015) B Lymphocytes: Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000914.pub3]