BAFFR (TNFRSF13C) and its ligand BAFF (TNFSF13B) are imperative for the normal development and survival of naïve B cells. In response to T-dependent antigens, differentiated germinal centre (GC) B cells and memory cells (MBC) maintain their surface BAFFR expression, but the precise contribution of BAFF-BAFFR signalling in controlling these responses is not well understood. Immunisation of BAFFR-deficient or BAFF-deficient mice initiate GC responses that fail to be sustained past 7-14 days and a marked absence of MBCs. However, since BAFFR-deficient or BAFF-deficient mice have structural abnormalities in their secondary lymphoid tissues, it remains unclear to what extent GC B cells and MBCs homeostasis depended on BAFF-BAFFR signalling.

To investigate this question, we performed adoptive transfer studies to examine the response of wild-type and BAFFR-deficient hen egg lysozyme-specific (SW_HEL) B cells in normal intact recipient mice.

Wild-type and BAFFR-deficient immature SW_HEL B cells formed intact GC responses that were sustained beyond 21 days. In addition, BAFFR-deficient GC B cells underwent normal Ig class-switching and affinity maturation. Furthermore, the absence of T cell-derived BAFF had no detectable impact on affinity-based selection in the GC. Interestingly, wild-type and BAFFR-deficient GC responses generated similar numbers of class-switched high affinity MBCs. These together suggest BAFF-BAFFR signalling has minimal impact in regulating GC survival and GC-derived memory output. However, we observed a significant loss of low affinity MBCs in BAFFR-deficient responses that were primarily unmutated. We found the overexpression of BAFFR on wild-type SW_HEL B cells also significantly increases the numbers of unmutated early MBCs. These findings suggest these unmutated MBCs are highly dependent on BAFFR-signalling, highlighting their distinctive survival requirements for BAFF in contrast to BAFF-independent MBCs that develop from GC precursors.