IgM-mediated signaling is required for the development of a normal B cell memory response

Abstract

Mature B cells co-express both IgM and IgD types of antigen receptors before activation. Our earlier work has shown that the co-expression of IgD and IgM plays an important role in regulating the composition of antibody repertoire during a primary immune response. However, the roles of these two B cell receptors in the development of B cell memory responses remain unclear. The present study shows that during the secondary immune response to (4-hydroxy-3-nitrophenyl)acetyl (NP), IgM -/-mice secreted significant amount of NP-specific IgD antibodies. The kinetics of antigenspecific IgD antibodies produced in IgM -/-mice was similar to that of IgM antibodies in wild type mice during the secondary response. However, the production of antigen specific class-switched antibodies in IgM -/-mice was significantly reduced compared to that in wild type mice, particularly at the early phase of the memory response. In addition, germinal center (GC) reaction was significantly diminished in IgM -/-mice after secondary challenge with soluble antigen. Nevertheless, affinity maturation of antibodies appears largely intact in IgM -/-mice during memory response. Thus, our studies demonstrate that IgM-mediated signaling plays an important role in the development of efficient B cell memory responses.

Opposing roles of IgM and IgD in BCR‐induced B‐cell survival

“…However, IgM-deficient mice had reduced IgD + CD5 + B-1a population in the peritoneal cavity (Lutz et al, 1998), which is typically observed in mice with reduced BCR signaling, indicating that IgD alone cannot generate a signal that is as strong as that in WT B cells. Consistently, IgM-deficient mice showed reduced or delayed Ab production against a T-D Ag and in response to virus infection (Guo, Zhang, Zheng, & Han, 2008;Han et al, 2004;Lutz et al, 1998). More importantly, the finding that IgD is able to function when IgM is absent does not necessarily mean that IgD has the same function when IgM is present.…”

IgM, FcμRs, and Malarial Immune Evasion

“…We have become intrigued by the possibility that these various DBL domains may interact directly with lgM + B cells through the B cell receptor (BCR), as Cμ4 specific mAbs that inhibit PfEMP1 binding to IgM have also been shown to augment S phase entry of human B cells via the lgM + BCR (16,49). IgM-mediated signaling is required for the development of a normal B-cell memory response (50). Our finding that malaria parasites, known to promote polyclonal B-cell activation, encode molecules specific for Cμ4 certainly suggests that binding to this region of the BCR might also be immunologically important and merits further investigation.…”