Il10

Increased MHC class II expression (mouse); proliferation, differentiation, Ig secretion (human)

TGFßR

Protein kinase

TGFß

Inhibition of growth; class switch to IgA, lgG2b

HCR, hematopoietic cytokine receptor; ICAM, intercellular adhesion molecule; IFN, interferon; Ig, immunoglobulin; IL, interleukin, LFA, leukocyte function antigen; MHC, major histocompatibility complex; TCR, T cell receptor; TGF, transforming growth factor; TNF, tumor necrosis factor.

HCR, hematopoietic cytokine receptor; ICAM, intercellular adhesion molecule; IFN, interferon; Ig, immunoglobulin; IL, interleukin, LFA, leukocyte function antigen; MHC, major histocompatibility complex; TCR, T cell receptor; TGF, transforming growth factor; TNF, tumor necrosis factor.

cells producing diverse Ig products. Diversity of the primary repertoire is generated in various ways: rearrangement of numerous Ig V gene segments without somatic mutations (fetal mice); similar rearrangements plus the addition of untemplated nucleotides at the junction of H gene segments (humans, postnatal mice); gene conversion with a smaller number of functional genes (rabbit, chicken); or mutation of functional genes (sheep ileal Peyer's patches). By the time the B cells emerge from the bursa or bone marrow, or shortly thereafter, the great potential diversity has been narrowed by elimination of cells making strongly autoreactive antibodies and by the short lifespan of cells that encounter no antigen. About 1.5 x 107 B cells are produced in adult mouse bone marrow daily; 10-15% of them survive to enter the total B cell pool, which totals about 5 x 108 cells. A significant fraction of neonatal IgM reacts both with bacterial antigens and, weakly, with autoantigens, as do IgM products of newly formed B cells through adult life. Normal regulatory processes, however, prevent the expansion of B cells that would produce large amounts of high-affinity autoantibodies of other Ig classes. When that regulation fails, autoantibody production is often associated with autoimmune disease.

In humans and mice a small subset of B cells expresses CD5 (Ly-1), a protein present on all T cells. CD5+ B cells are prominent in fetal and neonatal mice, in the peritoneum of adult mice, and among human fetal B cells and adult B cells that make natural autoantibodies. CD5 expression may be a reflection of how antigen stimulation occurs or a marker for a particular B cell lineage.

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