RESUMO
It has long been presumed that after leaving the germinal centers (GCs), memory B cells colonize the marginal zone or join the recirculating pool. Here we demonstrate the preferential localization of nitrophenol-chicken gamma-globulin-induced CD38(+)IgG1(+) memory B cells adjacent to contracted GCs in the spleen. The memory B cells in this region proliferated after secondary immunization, a response that was abolished by depletion of CD4(+) T cells. We also found that these IgG1(+) memory B cells could present antigen on their surface, and that this activity was required for their activation. These results implicate this peri-GC region as an important site for survival and reactivation of memory B cells.
Assuntos
Linfócitos B/imunologia , Centro Germinativo/imunologia , Imunoglobulina G/imunologia , Memória Imunológica/imunologia , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Animais , Linfócitos B/citologia , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Galinhas , Citometria de Fluxo , Centro Germinativo/metabolismo , Imunização , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Nitrofenóis/química , Fenilacetatos/química , Baço/citologia , Baço/imunologia , Baço/metabolismo , gama-Globulinas/química , gama-Globulinas/imunologiaRESUMO
The B cell antigen receptor (BCR)-mediated activation of IkappaB kinase (IKK) and nuclear factor-kappaB require protein kinase C (PKC)beta; however, the mechanism by which PKCbeta regulates IKK is unclear. Here, we demonstrate that another protein kinase, TGFbeta-activated kinase (TAK)1, is essential for IKK activation in response to BCR stimulation. TAK1 interacts with the phosphorylated CARMA1 (also known as caspase recruitment domain [CARD]11, Bimp3) and this interaction is mediated by PKCbeta. IKK is also recruited to the CARMA1-Bcl10-mucosal-associated lymphoid tissue 1 adaptor complex in a PKCbeta-dependent manner. Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCbeta, brings two key protein kinases, TAK1 and IKK, into close proximity, thereby allowing TAK1 to phosphorylate IKK.