Rituximab in rheumatic diseases.

Although B cells and T cells are indistinguishable from each other on a blood smear, their phenotypes are clearly different. Differences in membrane immunoglobulin expression were noted in early studies. Subsequently, the development of monoclonal antibodies led to the identification of cluster of differentiation (CD) molecules at the cell surface. The CD pattern can be used to characterize the cell type. For instance, T cells express CD2 and CD3, whereas B cells express CD19 and CD20. B cells originate in the bone marrow. Pro-B cells convert to pre-B cells via productive immunoglobulin gene rearrangement [1]. Pre-B cells migrate to secondary lymphoid organs where they become either resident cells (e.g., type 1 B cells in the serosa and B cells in the marginal zone) or nomadic cells (e.g., type 2 B cells in the germinal centers). Double labeling for IgD and CD38 can be used to separate germinal center B cells into important developmental stages from naive (Bm1) to activated (Bm2) B cells, germinal-center founder cells (Bm20), centroblasts (Bm3), centrocytes (Bm4), and memory cells (Bm5) and plasma cells (Table 1). B cells carry out three main functions. They contribute to organize the secondary lymphoid organs by producing tumor necrosis factor alpha (TNFa) and lymphotoxin. B cells can act as antigen-presenting cells, capturing and internalizing the antigen and presenting its remnants to T cells or to other B cells. Finally, B cells produce cytokines. Be1 cells chiefly produce interferon gamma and interleukin (IL)-2 and Be2 cells IL-4 and IL-6. One of the main unresolved issues regarding autoimmunity is the mechanism by which B cells lose their tolerance to selfantigens. Signaling by the antigen-linked BCR requires activation of the cell’s transduction machinery. When this process succeeds, B-cell proliferation ensues. The B-cell response threshold is controlled by facilitating factors (CD19 and CD21) and by anergy-inducing factors (CD5, CD22, CD32 and CD72). Furthermore, BCR specificity is not determined definitively in the bone marrow. Changes in BCR specificity may occur via rearrangement of genes for immunoglobulin