Figure 1. Characteristic plasma cell morphology shown of bone marrow plasma cells stained with haematoxylin and eosin.

Figure 2. Maturation and migration of developing B cells. B cells develop from haematopoietic stem cells found in the periphery of the bone marrow. Differentiation progresses from the periphery of the marrow towards the central sinus. Development requires specific cytokines produced by and contact provided by stromal cells as indicated. Developing B cells are retained in the bone marrow (and restricted from early release) by chemokines produced primarily by stromal cells, namely CXCL12. Developing B cells express CXCR4, the receptor for CXCL12 on their surface. Once the immature B-cell stage is reached, the cells lose expression of CXCR4 and are released into the central sinus where they migrate to secondary lymphoid tissue. Plasmablasts entering the bone marrow from the secondary lymphoid tissue similarly find stromal cells to support their longevity. Again, stromal cells provide soluble factors necessary for retention and survival in the marrow, such as IL-6 and CXCL12. While contact is needed for plasma cell survival, the adhesion event is unclear; however, VCAM-1 is dispensable.

Figure 3. Schematic of plasma cell development and resultant phenotype. Naive B cells stimulated with antigen form antibody-secreting, proliferation-capable plasmablasts. Provided with the appropriate cues, plasmablasts develop into terminally differentiated plasma cells. Plasma cells express Syndecan-1 (CD138), CD44 and VLA-4 on their surface (among others); they downregulate expression of MHC Class II, B220 and the BCR complex. Further, plasma cells express Blimp-1 and XBP-1, which results in the inhibition of proliferation and of Pax-5 expression, among others (see Figure 4).

Figure 4. A simplified model of the regulatory cascades initiated during plasma cell differentiation. Targets activated by a particular factor are indicated by arrows; targets repressed are indicated by bars.

Figure 5. A model of the elements necessary for maintaining plasma cell survival. Plasma cells and stromal cells interact in the bone marrow via VLA-4 on the plasma cell and an unknown ligand on the stromal cell. Contact induces the expression of IL-6 mRNA and consequently IL-6 secretion, which is critical to maintain plasma cell longevity. Further, stromal cells secrete CXCL12, which is important for attracting plasmablasts to the marrow, for retention of plasma cells in the marrow, and possibly for maintaining plasma cell survival.