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

The B‐cell receptor (BCR) transmits a tonic survival signal in the absence of antigen stimulation and an antigen‐triggered survival signal. Mature B cells express two types of BCR, IgM and IgD, but it remains unclear how B‐cell survival is differentially regulated by these two receptors. We found that, whereas cross‐linking IgM on spleen B cells greatly enhanced their survival, cross‐linking IgD did not enhance, but rather decreased, their survival. Consistently, cross‐linking both IgM and IgD only moderately enhanced B‐cell survival, suggesting that IgM and IgD play opposing roles in B‐cell survival induced by BCR stimulation. Based on these and additional experimental results, we present a mathematical model integrating IgM‐ and IgD‐mediated survival signals. Our model shows that IgD can transmit a tonic survival signal in the absence of antigen stimulation but cross‐linking IgD not only does not generate a survival signal but also disrupts its tonic signal, resulting in inhibition of B‐cell survival. These results suggest that IgD attenuates BCR‐induced survival in mature B cells, presumably to restrain B‐cell response to weak and/or self‐antigens and prevent nonspecific B‐cell activation and autoimmunity.