The B-cell antigen receptor (BCR) complex of mature B cells is composed of membrane Ig molecules and the associated Igα and Igβ proteins and serves two key roles in B-cell activation. First, the binding of antigen to the receptor delivers biochemical signals to the B cells that initiate the process of activation. As discussed later, signaling is more robust with multivalent T-independent antigens than with T-dependent protein anti gens. Antigen-induced biochemical signals are initiated by SRC family kinase–mediated phosphorylation of the ITAM tyrosines of Igα and Igβ, followed by the recruitment and activation of SYK. Second, the receptor internalizes the bound antigen into endosomal vesicles, and if the antigen is a protein, it is processed into peptides that bind to MHC class II molecules and may be presented on the B-cell surface for recognition by helper T cells. This antigen-presenting function of B cells will be considered later in the context of T-dependent B-cell activation.
The interaction of different types of antigens (multivalent molecules or proteins) with the BCR initiates B-cell proliferation and differentiation in different ways. The importance of signaling by the BCR complex for the subsequent responses of the cells varies with the nature of the antigen. Most T-independent antigens, such as polysaccharides, contain multiple identical epi topes on each molecule. Such multivalent antigens can effectively cross-link many B-cell antigen receptors on a single B cell and initiate responses of that cell even though the antigens are not recognized by helper T lymphocytes. In contrast, many naturally occurring globular protein antigens possess only one copy of each epitope per molecule. Therefore, such protein antigens, in their functionally monovalent form, cannot simultaneously bind to and cross-link multiple Ig molecules, and their ability to directly activate the BCR is limited; they do not typically induce signals that can drive B-cell proliferation and differentiation. These weak signals may be sufficient to keep the B cells alive, induce changes in chemokine receptor expression, and promote antigen endo cytosis. Some protein antigens may be displayed as multivalent arrays on the surfaces of microbes or host cells such as FDCs, or they may be multivalent because they are in aggregates.
Although antigen recognition can initiate B-cell responses, by itself it is usually inadequate to stimulate significant B-cell proliferation and differentiation, even for T-independent anti gens. For full responses to be induced, other stimuli cooperate with BCR engagement, including complement proteins, innate pattern recognition receptors, and, in the case of protein anti gens, helper T cells (discussed later).
