Enhanced BCR signaling inflicts early plasmablast and germinal center B cell death

Abstract

It is still not clear how B cell receptor (BCR) signaling intensity affects plasma cell (PC) and germinal center (GC) B cell differentiation. We generated Cγ1 ^{<i>Cre/wt</i>} Ptpn6 ^<i>fl/fl</i> mice where SHP-1, a negative regulator of BCR signaling, is deleted rapidly after B cell activation. Although immunization with T-dependent antigens increased BCR signaling, it led to PC reduction and increased apoptosis. Dependent on the antigen, the early GC B cell response was equally reduced and apoptosis increased. At the same time, a higher proportion of GC B cells expressed cMYC, suggesting GC B cell-Tfh cell interactions may be increased. GC B cell numbers returned to normal at later stages, whereas affinity maturation was suppressed in the long term. This confirms that BCR signaling not only directs affinity-dependent B cell selection but also, without adequate further stimulation, can inflict cell death, which may be important for the maintenance of B cell tolerance.