RESUMO
We analyzed here the expression of the prosurvival Bcl-2 homologue A1 in peripheral B cell compartment. We observed that A1 mRNA are highly expressed in peripheral B cells as compared with other anti-apoptotic genes of the Bcl-2 family such as bcl-xl and bcl-2 itself. The expression of A1 is up-regulated in immature B cells at the transition between transitional type 1 (T1) and type 2 (T2) cells, and remained highly expressed in mature (M) B cells. We, therefore, analyzed the effect of B cell antigen receptor (BCR) and BAFF receptor (BAFF-R) engagement on the regulation of A1 in total B220(+) cells but also FACS-sorted immature T1, T2 and M B cells. We demonstrated that only BCR engagement up-regulated the expression of A1 mRNA and protein. These results suggest that A1 may play a key role in antigen-dependent signals that are required for survival and/or proliferation of peripheral B cells.
Assuntos
Apoptose , Linfócitos B/metabolismo , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Baço/citologia , Animais , Receptor do Fator Ativador de Células B , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Antígenos de Histocompatibilidade Menor , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo , Proteína bcl-XRESUMO
The anti-proliferative effect of Bcl-2 acts mainly at the level of the G0/G1 phase of the cell cycle. Deletions and point mutations in the bcl-2 gene show that the anti-proliferative activity of Bcl-2, can in some cases, be dissociated from its anti-apoptotic function. This indicates that the effect of Bcl-2 on cell cycle progression can be a direct effect and not only a consequence of its anti-apoptotic activity. Bcl-2 appears to mediate its anti-proliferative effect by acting on both signal transduction pathways (NFAT, ERK) and on specific cell cycle regulators (p27, p130).
Assuntos
Divisão Celular/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Sequência de Aminoácidos , Animais , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Humanos , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-bcl-2/química , Transdução de SinaisRESUMO
We have studied the impact of B-cell receptor (BCR) or CD40 ligation on the in vitro chemotactic response of tonsillar B cells to 4 chemokines: stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and B-cell-attracting chemokine (BCA)-1. In the tonsil, SDF-1 and MIP-3alpha are both expressed in the crypt epithelium, while MIP-3beta is found in the T zone and BCA-1 in the follicles. Resting virgin and memory B cells display a similar chemotaxis pattern, and they both have the potential to migrate in vitro to all 4 chemokines studied. This pattern of responsiveness is strongly modified by a surrogate antigen (Ag) but is not altered by CD40 ligand. We report here that surrogate Ag induces a profound and sustained suppression of the response to the crypt chemokines SDF-1alpha and MIP-3alpha, while it exacerbates the migratory response to MIP-3beta. The effect of surrogate Ag on the response to BCA-1 is biphasic: After an initial phase of suppression, chemotaxis toward BCA-1 is strongly up-regulated. Our results suggest that Ag is primarily responsible for reprogramming the B-cell chemotaxis responsiveness during the humoral response. We propose that it initiates an ordered change of the chemotaxis machinery allowing Ag-activated B cells to relocate in the T zone and B-cell follicles sequentially.