RESUMEN
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.
Asunto(s)
Linfocitos B/inmunología , Centro Germinal/inmunología , Inmunoglobulina G/inmunología , Memoria Inmunológica/inmunología , ADP-Ribosil Ciclasa 1/inmunología , ADP-Ribosil Ciclasa 1/metabolismo , Animales , Linfocitos B/citología , Linfocitos B/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Pollos , Citometría de Flujo , Centro Germinal/metabolismo , Inmunización , Inmunoglobulina G/genética , Inmunoglobulina G/metabolismo , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Nitrofenoles/química , Fenilacetatos/química , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , gammaglobulinas/química , gammaglobulinas/inmunologíaRESUMEN
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.