Fig. 2. B-cell differentiation pathway. Pre-B cells characterized by intracytoplasmic immunoglobulin M (IgM) heavy chain (cμ) differentiate into immature B cells. These B cells are the first cells to reproduce light chains, which can then combine with the μ heavy chain to become expressed as IgM on the cell surface. The immature B cell differentiates into a mature B cell, which expresses both IgM and immunoglobulin D (IgD) on its cell surface. This part of the differentiation process does not require antigen and is referred to as antigen independent. On contact with the specific antigen via the surface immunoglobulin, the mature B cell becomes activated. Together with helper T cells (CD4+ ) and interleukins/cytokines derived from T cells and monocytes, the activated B cell matures into a plasma cell to produce immunoglobulins of a single isotype (Y). However, an antigen stimulates a polyclonal B-cell response, which results in many plasma cells and immunoglobulin production of several classes or isotypes. (After Medical Knowledge Self-Assessment Program [MKSAP]: Allergy and Immunology, Book 1, p 155. Philadelphia: American College of Physicians, 1993.)