B cells in autoimmunity

Abstract

B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have expanded our understanding of effector functions of B cells as well as their roles in human autoimmune diseases. The current review addresses the role of certain stages of B-cell development as well as plasmablasts/plasma cells in immune regulation under normal and autoimmune conditions with particular emphasis on systemic lupus erythematosus. Based on preclinical and clinical data, B cells have emerged increasingly as both effector cells as well as cells with immunoregulatory potential.

Figure 1

Schematic B-cell development of B2 B cells emigrating as immature B cells from the bone marrow and differentiating further into naïve/marginal zone (MZ) B cells in the spleen, which subsequently undergo T cell-dependent differentiation into memory B cells and plasma cells. Secondary lymphoid tissue refers to spleen, tonsil, lymph node, and Peyer's patches. CSR, class-switch recombination; GC, germinal center; MALT, mucosal-associated lymphoid tissue; NF, nuclear factor expression; PC, plasma cells; SC, stem cell; SHM, somatic hypermutation; T1, transitional 1; T2, transitional 2.

Figure 2

Major differences of peripheral B-cell compartments between systemic lupus erythematosus (SLE) patients and normal controls as shown in a representative dot plot. Please note the increased frequency of Ig-class-switched CD27⁺ memory B cells and CD27^-/IgD^- B cells. ND, normal donors.

Figure 3

CD27⁺ B cells with a memory phenotype are less susceptible to cyclophosphamide treatment in patients with systemic lupus erythematosus (SLE) (n = 20). Severely active SLE patients undergoing monthly intravenous cyclophosphamide bolus therapy were followed for a period of 3 to 6 months. Whereas CD27^- B cells and CD27⁺⁺ plasmablasts/plasma cells showed a decrease, the absolute numbers of CD27⁺ memory B cells did not change significantly. n.s., not significant.