Cytokines involved in B-cell differentiation and their sites of action

B cells originate from pluripotent hematopoietic stem cells and differentiate in the bone marrow into mature B cells. The differentiation of a stem cell into a mature B cell can be subdivided into five steps: early pro-B cells, late pro-B cell stage, pre-B cell stage, immature B cells, and mature B cells. Each differentiation step appears to be regulated by co-receptor and cytokines. The earliest B-cell progenitors are bound to the stromal cell surface by adhesive interactions through cell surface molecules to promote the binding of c-kit to stem cell factor (SCF). At the late pro-B cell stage, interleukin-7 (IL-7) induces proliferation and differentiation of pro-B cells to pre-B cells. Surface Ig-expressing mature B cells leave bone marrow and circulate into peripheral lymphoid organs in which they can be activated to proliferate and to differentiate into antibody-secreting cells by encountering antigens and "helper" T (TH) cells. TH cells activate B cells by their products, cytokines such as IL-4, IL-5, and IL-6, and membrane-bound stimulatory molecules including CD40 ligand. Each cytokine has pleiotropic activity on B cells and other cell types, and acts through a specific receptor. Abnormal expression of a cytokine receptor and aberrant signal transduction causes functional abnormality of B cells.