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, 118 (4), 429-37

The Riddle of the Dual Expression of IgM and IgD


The Riddle of the Dual Expression of IgM and IgD

Roland Geisberger et al. Immunology.


Signalling through the B cell antigen receptor (BCR) is required for peripheral B lymphocyte maturation, maintenance, activation and silencing. In mature B cells, the antigen receptor normally consists of two isotypes, membrane IgM and IgD (mIgM, mIgD). Although the signals initiated from both isotypes differ in kinetics and intensity, in vivo, the BCR of either isotype seems to be able to compensate for the loss of the other, reflected by the mild phenotypes of mice deficient for mIgM or mIgD. Thus, it is still unclear why mature B cells need expression of mIgD in addition to mIgM. In the current review we suggest that the view that IgD has a simply definable function centred around the basic signalling function should be replaced by the assumption that IgD fine tunes humoral responses, modulates B cell selection and homeostasis and thus shapes the B cell repertoire, defining IgD to be a key modulator of the humoral immune response.


Figure 1
Figure 1
The level of surface IgM expression (left scale) is set according to the specificity of the IgM towards self-tissue (right scale) and thus according to the signal strength (x-axis). The higher the degree of self-reactivity, the higher is the degree of IgM down-regulation. However, when the number of IgM molecules is beyond the threshold for survival (marked with an x), anergy (lower scattered line) or apoptosis (upper scattered line) is initiated, respectively. The left diagram illustrates the IgD knockout, showing that self reactivity readily leads to IgM down-regulation and commitment to negative selection (a). In the wild type (b) IgD expression in addition to surface IgM allows positive selection of B-cell clones with higher self-specificity. Putatively, signals from IgD are modulated and diminished through influence of IgM. This mechanism could transform relatively high degrees of receptor engagement into moderate levels of BCR signalling, allowing survival and positive selection.

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