FcμR enhances recall responses by promoting the generation of CD80+PD-L2+ memory B cells.

The IgM Fc receptor (FcμR), the sole receptor specific for IgM, is crucial for B cell survival and humoral immunity. Yet, its role in memory B cells (MBCs) has remained unclear. Here, we show that FcμR-/- mice immunized with the T-dependent antigen 4-hydroxy-3-nitrophenyl acetyl-chicken γ-globulin (NP-CGG) generate normal numbers of IgG1+ MBCs with long-term survival comparable to that of WT mice. However, the IgG1+ MBCs in FcμR-/- mice contained a reduced proportion of mature CD80+PD-L2+ cells, a subset associated with potent recall responses and plasma cell differentiation. Consistently, adoptive transfer of NP-specific MBCs and CGG-specific memory T cells into Rag1-/- mice revealed significantly diminished memory B cell responses in recipients of FcμR-/- MBCs. Mechanistically, FcμR-/- IgG1+ MBCs exhibited impaired B cell receptor signaling and reduced activation of transcription factors essential for plasma cell differentiation upon antigen re-challenge both in vivo and in vitro. Together, these findings establish FcμR as a previously unrecognized key regulator of CD80+PD-L2+ MBC formation and recall responses.