{Reference Type}: Journal Article {Title}: T cell help to B cells: Cognate and atypical interactions in peripheral and intestinal lymphoid tissues. {Author}: Biram A;Shulman Z; {Journal}: Immunol Rev {Volume}: 296 {Issue}: 1 {Year}: 07 2020 {Factor}: 10.983 {DOI}: 10.1111/imr.12890 {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.