Antigen and cytokine receptor signals guide the development of the na⟨ve mature B cell repertoire

Immature B cells are generated daily in the bone marrow tissue. More than half of the newly generated immature B cells are autoreactive and bind a self-antigen, while the others are nonautoreactive. A selection process has evolved on the one hand to thwart development of autoreactive immature B cells and, on the other hand, to promote further differentiation of nonautoreactive immature B cells into transitional and mature B cells. These negative and positive selection events are carefully regulated by signals that emanate from the antigen receptor, whether antigen-mediated or tonic, and are influenced by signals that are generated by receptors that bind cytokines, chemokines, and other factors produced in the bone marrow tissue. These signals, therefore, are the predominant driving forces for the generation of a B cell population that is capable of protecting the body from infections while maintaining self-tolerance. Here, we review recent findings from our group and others that describe how tonic antigen receptor signaling and bone marrow cytokines regulate the selection of immature B cells.