| First Author | Pappu BP | Year | 2006 |
| Journal | Eur J Immunol | Volume | 36 |
| Issue | 11 | Pages | 3033-43 |
| PubMed ID | 17048267 | Mgi Jnum | J:117002 |
| Mgi Id | MGI:3695357 | Doi | 10.1002/eji.200535663 |
| Citation | Pappu BP, et al. (2006) Potential role of CARMA1 in CD40-induced splenic B cell proliferation and marginal zone B cell maturation. Eur J Immunol 36(11):3033-43 |
| abstractText | NF-kappaB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen-mediated activation of B cells. CARD domain and MAGUK-domain containing protein-1 (CARMA1), recently identified adaptor molecule, has been shown to play an essential role in BCR-induced NF-kappaB activation. CARMA1-deficient B cells fail to proliferate upon BCR stimulation, leading to defective humoral responses. Surprisingly, CARMA1-deficient B cells are also defective in CD40-induced proliferation. The mechanisms responsible for CD40-induced proliferation defect have not yet been characterized. In this study, we show that signaling cascades activated by CD40 stimulation are largely unaffected in CARMA1-deficient B cells. Instead, we have found that the defective proliferation of CARMA1-deficient B cells is due to two events. First, CARMA1-deficient B cells show defective cell-cycle progression. Secondly, the numbers of marginal zone (MZ) B cells, which are the main responders upon CD40 stimulation, are greatly diminished in CARMA1-deficient mice. Since B cell maturation requires basal signaling through BCR and NF-kappaB activation, we propose that impaired BCR signaling in CARMA1-deficient mice leads to defective maturation of MZ B cell population, which in turn, contributes to impaired proliferation upon CD40 stimulation. |
