T cell help to B cells: Cognate and atypical interactions in peripheral and intestinal lymphoid tissues

Abstract Enduring immunity against harmful pathogens depends on the generation of immunological memory. Serum immunoglobulins are constantly secreted by long‐lived antibody‐producing cells, which provide extended protection from recurrent exposures. These cells originate mainly from germinal center structures, wherein B cells introduce mutations to their immunoglobulin genes followed by affinity‐based selection. Generation of high‐affinity antibodies relies on physical contacts between T and B cells, a process that facilitates the delivery of fate decision signals. T‐B cellular engagements are mediated through interactions between the T cell receptor and its cognate peptide presented on B cell major histocompatibility class II molecules. Here, we describe the cellular and molecular aspects of these cognate T‐B interactions, and highlight exceptional cases, especially those arising at intestinal lymphoid organs, at which T cells provide help to B cells in an atypical manner, independent of T cell specificity.