Potential role of CARMA1 in CD40-induced splenic B cell proliferation and marginal zone B cell maturation
| Autor: | Xin Lin, Bhanu P. Pappu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Immunology
B-cell receptor Naive B cell Apoptosis Lymphocyte Activation Mice Cell Movement Marginal zone B-cell medicine Animals Immunology and Allergy CD40 Antigens B cell Cell Proliferation Mice Knockout Mitogen-Activated Protein Kinase Kinases B-Lymphocytes CD40 biology Cell growth Cell Cycle NF-kappa B Cell cycle Marginal zone Cell biology CARD Signaling Adaptor Proteins medicine.anatomical_structure biology.protein Apoptosis Regulatory Proteins Spleen |
| Zdroj: | European Journal of Immunology. 36:3033-3043 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200535663 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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