Analysis of the individual contributions of Igα (CD79a)- and Igβ (CD79b)-mediated tonic signaling for bone marrow B cell development and peripheral B cell maturation

The individual contribution of Ig alpha and Ig beta for BCR-triggered fates is unclear. Prior evidence supports conflicting ideas concerning unique as well as redundant functions for these proteins in the context of BCR/pre-BCR signaling. Part of this ambiguity may reflect the recent appreciation that Iga and Ig beta participate in both Ag-independent (tonic) and Ag-dependent signaling. The present study undertook defining the individual requirement for Iga and Ig beta under conditions where only ligand-independent tonic signaling was operative. In this regard, we have constructed chimeric proteins containing one or two copies of the cytoplasmic domains of either Iga or Ig beta and Ig alpha/Ig beta heterodimers with targeted Tyr -> Phe modifications. The ability of these proteins to act as surrogate receptors and trigger early bone marrow and peripheral B cell maturation was tested in RAG2(-/-) primary pro-B cell lines and in gene transfer experiments in the mu MT mouse model. We considered that the threshold for a functional activity mediated by the pre-BCR/BCR might only be reached when two functional copies of the Ig alpha/Ig beta ITAM domain are expressed together, and therefore the specificity conferred by these proteins can only be observed in these conditions. We found that the ligand-independent tonic signal is sufficient to drive development into mature follicular B cells and both Iga and Ig beta chains supported formation of this population. In contrast, neither marginal zone nor B1 mature B cell subsets develop from bone marrow precursors under conditions where only tonic signals are generated.