Bursa of Fabricius

Abstract

The bursa of Fabricius plays a central role in the development of the antibody‐producing B‐lymphocyte lineage in birds. It consists of more than 10 000 follicles surrounded by connective tissue. These follicles provide an appropriate microenvironment for generating a primary repertoire of antibodies. Immunoglobulin gene diversification is achieved by gene conversion and is antigen independent. Follicular B cells undergo very rapid cell division while expressing several genes also expressed in proliferating germinal centre B cells, such as AID, UNG, Pax5 and Bcl6. Bursal B cell line DT40 provides a unique model system for gene‐targeting studies clarifying the B‐cell development, function and Ig diversification.

Key Concepts:

  • Bursa of Fabricius is the primary site for B‐cell development and antibody repertoire formation in birds.

  • Antibody diversification in the bursa of Fabricius is antigen independent and occurs mostly by Ig gene conversion.

  • Bursal derived DT40 B cell line provides a reverse genetic model to study molecular function of B cells.

Keywords: aves; B cells; Ig diversification; gene conversion; haematopoiesis; DT40; evolution

Figure 1.

Anatomy and structure of the avian bursa of Fabricius. (a) Anatomical location of the chicken thymus and the bursa of Fabricius, and a cross‐section of the bursa of Fabricius. The bursa has a highly folded surface surrounding the central lumen, which is connected to the intestine by the bursal duct. The lymphoid follicles are situated within the longitudinal plicae. Altogether, the bursa contains approximately 10 000 follicles. Between the bursal medulla and lumen is the follicular‐associated epithelium (FAE). (b) Avian B‐cell development. The progenitor cells seeding the bursal primordium originate from the paraaortic mesenchyme. These prebursal ‘stem cells’ (prebursal B‐cell progenitors) are committed to the B‐cell lineage before bursal colonisation. Within the bursal follicles the surface immunoglobulin‐expressing bursal progenitors start to divide and diversify their immunoglobulin V genes. The proliferating bursal B cells are densely packed in the cortical part of the bursal follicles. The medulla (M) contains mainly loosely packed lymphocytes and stromal cells. Starting shortly before hatching, diversified B cells start to emigrate from the bursa; however, more than 95% of bursal B cells die by apoptosis. Within the peripheral lymphoid organs, postbursal B cells can further modify their immunoglobulin gene specificity by gene conversion and by somatic hypermutation. The peripheral lymphoid organs cannot, however, replace the important function of the bursa as a mutant‐generating organ.

Figure 2.

Schematic comparison of human and avian B‐cell development. In human (and mouse) B cells develop in the fetal liver and bone marrow. During pro‐B cell stage Ig heavy chains (IgH) are rearranged and expressed on the cell surface with surrogate light chains as part of a pre‐BCR complex. Following Ig light (IgL) chain rearrangement leads to the expression of completed IgM on the cell surface of immature B cells. Owing to the multiple Ig V(D)J regions multitude IgMs with variable specificity are generated. In contrast, birds recombine IgH and IgL chains simultaneously during the prebursal development and no considerable variation in Ig specificity is generated. The Ig diversity is primarily achieved by gene conversion and to lesser extent by somatic hypermutation (SHM) at the bursal stage of the development. SHM further adds variability to Ig specificity at the stage of germinal centre (GC) B cells in both human and birds, but in avian GCs also Ig gene conversion occurs at early stages of GC development.

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Further Reading

Arakawa H and Buerstedde JM (2004) Immunoglobulin gene conversion: insights from bursal B cells and the DT40 cell line. Developmental Dynamics 229: 458–464.

Brown WRA, Hubbard SJ, Tickle C and Wilson SA (2003) The chicken as a model for large‐scale analysis of vertebrate gene function. Nature Reviews. Genetics 4: 87–98.

Buerstedde JM and Takeda S (eds) (2006) Reviews and Protocols in DT40 Research. Subcellular Biochemistry, vol 40. New York: Springer. ISBN 978‐1402048951.

McCormack WT, Tjoelker LW and Thompson CM (1991) Avian B‐cell development: generation of an immunoglobulin repertoire by gene conversion. Annual Review of Immunology 9: 219–241.

Weill JC and Reynaud CA (1987) The chicken B cell compartment. Science 238(4830): 1094–1098.

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Mustonen, Laura, Alinikula, Jukka, Lassila, Olli, and Nera, Kalle‐Pekka(Sep 2010) Bursa of Fabricius. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000506.pub3]