Class II MHC cytoplasmic domain-mediated signaling in B cells: A tail of two signals

In addition to their role in antigen presentation, class II MHC molecules also transmit signals to B lymphocytes. Class II MHC-mediated signals initiate a range of events in B cells, including induction of cell surface proteins, initiation of cell-cycle progression/proliferation, activation of or protection from apoptosis, and antigen-dependent plasma cell differentiation. Although various transmembrane signaling proteins associate with class II MHC molecules, the class II MHC cytoplasmic domains are essential for signals leading to increased intracellular cAMP and activation of protein kinase C (PKC). Although truncation and mutagenesis studies have provided considerable information about the cytoplasmic domain sequences required, how class II MHC molecules elicit cAMP and PKC activation is not known. Further, appropriate T-dependent B cell responses require intact cAMP and PKC signaling, but the extent to which class II MHC signals are involved is also unknown. This review details our current knowledge of class II MHC cytoplasmic domain signaling in B cells with an emphasis on the likely importance of class II MHC signals for T-dependent antibody responses.