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- W4313385514 abstract "Abstract There are conflicting reports on the role of CD40 signaling in the initiation and maintenance of germinal centers (GC). CD40 signaling invokes the nuclear translocation of RelB, a transcription factor that promotes IRF4 expression. We examined the early stages of GC B cell differentiation without any phenotypic preconceptions by the adoptive transfer of tagged antigen-specific B cells. As expected, B cells were first observed to express intermediate levels of BCL6 within the interfollicular (IF) zone shortly after immunization. However, these GC B cell precursors had only a partial GC phenotype and co-expressed RelB and IRF4, transcription factors known to repress BCL6 transcription. This initial co-expression of mutually antagonistic transcription factors is short-lived: follicular BCL6hi GC B cells with diminished levels of RelB and IRF4 emerge shortly thereafter, coupled with the disappearance of the immediate precursors as a function of cell division. Interestingly, potentiating T cell help at the GC initiation stage blocks this transition and diverts the fate of GC immediate precursors towards plasma cells, suggesting that ongoing T cell engagement discourages GC B cell formation. Consistent with this idea, we found that reducing the amount of antigen at the time of immunization accelerates GC B cell formation. Similarly, discontinuing T-cell derived factors in an in-vitro culture system promotes the generation of BCL6hi RelB− IRF4− cells with GC B cell properties. Taken together these results suggest that CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, but transition to the BCL6hi follicular state is completed by a period of abstinence from Th cell CD40L." @default.
- W4313385514 created "2023-01-06" @default.
- W4313385514 creator A5007105182 @default.
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- W4313385514 date "2016-05-01" @default.
- W4313385514 modified "2023-10-16" @default.
- W4313385514 title "Step-wise formation of germinal center B cells is completed by a requisite phase of Th cell disengagement and CD40 signaling abstinence" @default.
- W4313385514 doi "https://doi.org/10.4049/jimmunol.196.supp.195.3" @default.
- W4313385514 hasPublicationYear "2016" @default.
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