Signaling thresholds and interclonal competition in preimmune B-cell selection

Abstract

The need to eliminate autoreactive B cells must be checked against the need for a diverse B-cell repertoire. Protein tyrosine phosphatases SHP1 and CD45 act antagonistically within B cells to set the threshold level of antigen-receptor engagement required for B-cell elimination. The fate of B cells binding weak autoantigens is also regulated by interclonal competition. In the presence of a normal diverse repertoire of competitor B cells, the autoantigen-binding cells are excluded from follicles in spleen and lymph nodes and undergo rapid cell death. In the absence of interclonal competition, the autoreactive cells enter the follicular microenvironment and survive. A model in which B cells compete for access to limiting follicular niches in order to survive is discussed.