The process during which a B lymphocyte, after ligation of the antigen receptor, differentiates into a high-rate antibody-secreting plasma cell is under strict regulatory control of T lymphocytes and their soluble products. For most so-called T-cell-dependent (protein) antigens, antigen-specific CD4-positive T cells or T-cell factors participate in the transition of resting into activated B cell. Terminal B-cell differentiation, including immunoglobulin class switch, is regulated by a variety of (antigen non-specific) cytokines which act in a highly coordinated fashion. The other major class of naturally occurring antigens, the so-called T-cell independent (polysaccharide) antigens, apparently can induce B-cell activation in the absence of antigen-specific CD4-positive T cells. Terminal B-cell differentiation, however, also depends on the action of cytokines, although the relative contribution of individual cytokines remains to be determined. Downregulation of both T-cell-dependent and T-cell independent antigens is mediated by specific suppressor T cells. Next to this "internal control" by regulatory T cells, it is important to realize that components of the (neuro-)endocrine system (such as the endorphins and the family of insulin-like growth factors) and the complement system also exert important immunoregulatory functions.