The Humoral Immune Response to T Cell–Independent Antigens

T cell–independent (TI) antigens, often polysaccharides, are large multivalent molecules that elicit specific antibody responses in the absence of T cells. Since they are present on the surface of numerous pathogens, the mechanism by which they induce antibody responses must also be understood within the context of the pathogens that express them. TI antigens uniquely promote sustained and potent B cell receptor (BCR)-mediated signaling at low antigen concentrations through induction of multiple domains of highly cross-linked membrane immunoglobulin. Co-cross-linking of the BCR and the complement receptor (CD21) by complement-bound TI antigens further lowers the concentration of antigen required for effective BCR-mediated signaling. Multivalent BCR cross-linking alone appears to stimulate only B cell proliferation, necessitating ‘second signals’ for induction of Ig secretion and class switching. Molecules expressed on the pathogen surface that stimulate innate immunity can provide these second signals. Although antibody responses to TI antigens do not require T cell help, T cells can play a major role in augmenting these responses, especially when the TI antigen is expressed by an intact pathogen. A small subgroup of polysaccharides termed ‘zwitterionic’ have the unique ability to be presented on MHC-II molecules and thus directly recruit cognate CD4+ T cell help.