| First Author | Fuentes-Pananá EM | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 11 | Pages | 7913-22 |
| PubMed ID | 17114463 | Mgi Jnum | J:140691 |
| Mgi Id | MGI:3814306 | Doi | 10.4049/jimmunol.177.11.7913 |
| Citation | Fuentes-Panana EM, et al. (2006) Analysis of the individual contributions of Igalpha (CD79a)- and Igbeta (CD79b)-mediated tonic signaling for bone marrow B cell development and peripheral B cell maturation. J Immunol 177(11):7913-22 |
| abstractText | The individual contribution of Igalpha and Igbeta 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 Igalpha and Igbeta participate in both Ag-independent (tonic) and Ag-dependent signaling. The present study undertook defining the individual requirement for Igalpha and Igbeta 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 Igalpha or Igbeta and Igalpha/Igbeta 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 muMT 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 Igalpha/Igbeta 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 Igalpha and Igbeta 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. |
