B cells recognize antigen by means of membrane-bound antibody of the immunoglobulin M (IgM) class, expressed on the surface together with signaling molecules to form the B-cell receptor (BCR) complex (
Fig. 5.7 ). Whereas T cells recognize only MHC-associated peptides, B cells recognize and respond to many more chemical structures, including soluble or cell-associated proteins, lipids, polysaccharides, nucleic acids, and small chemicals, without a requirement for the MHC. As with TCRs, each antibody has a unique amino acid sequence. This sequence diversity is a consequence of the rearrangement and assembly of a multitude of immunoglobulin (Ig) gene segments, a process that creates functional Ig genes. B cells express several invariant molecules that are responsible for signal transduction and B-cell activation (see
Fig. 5.7 ). Some are signaling molecules attached to the BCR; another example is CD21 (also known as the type 2 complement receptor, or CR2), which recognizes a complement breakdown product that frequently is deposited on microbes and promotes B-cell responses to microbial antigens. Interestingly, the ubiquitous Epstein-Barr virus has cleverly evolved to use CD21 as a receptor for binding to B cells and infecting them.
After stimulation, B cells differentiate into plasma cells, which secrete large amounts of antibodies. There are five classes, or isotypes, of immunoglobulins: IgG, IgM, and IgA constitute more than 95% of circulating antibodies. IgA is the major isotype in mucosal secretions; IgE is present in
Fig. 5.7 StructureofantibodiesandtheB-cellantigenreceptor.(A)TheB-cellantigenreceptorcomplexiscomposedofmembraneimmunoglobulinM(IgM;orIgD,not shown),whichrecognizesantigens,andtheassociatedsignalingproteinsIgα andIgβ.CD21isareceptorforacomplementcomponentthatalsopromotesB-cellactivation.(B)CrystalstructureofasecretedIgGmolecule,showingthearrangementofthevariable(V)andconstant(C)regionsoftheheavy(H)andlight(L)chains.(Courtesy of Dr. Alex McPherson, University of California, Irvine, California.) the circulation at very low concentrations and also is found attached to the surfaces of tissue mast cells; and IgD is expressed on the surfaces of B cells but is secreted at very low levels. These isotypes differ in their ability to activate complement and recruit inflammatory cells, and thus have different roles in host defense and disease states.
NK cells are lymphocytes that arise from the same common lymphoid progenitor that gives rise to T lymphocytes and B lymphocytes. However, NK cells are innate immune cells, as they are functional without prior activation and do not express highly variable and clonally distributed receptors for antigens. Instead, NK cells have two types of receptors—inhibitory and activating. Inhibitory receptors recognize self class I MHC molecules, which are expressed on all healthy cells, whereas activating receptors recognize molecules that are expressed or upregulated on stressed or infected cells. Normally, the effects of inhibitory receptors dominate over those of activating receptors, preventing spontaneous activation of the NK cells. Infections (especially viral infections) and stress are associated with reduced expression of class I MHC molecules and increased expression of proteins that engage activating receptors. The net result is that the NK cells are activated and the infected or stressed cells are killed and eliminated. NK cells also secrete cytokines such as interferon-γ (IFN-γ), which activates macrophages to destroy ingested microbes, and thus NK cells provide early defense against intracellular microbial infections.