B ‐cell‐intrinsic STAT 6 signaling controls germinal center formation

Infection with helminths and exposure to antigens induce a strong type 2 immune response resulting in the secretion of the cytokines IL ‐4 and IL ‐13 by CD 4 + T cells and several innate cell types. IL ‐4 and IL ‐13 promote class switch recombination to I g G 1 and I g E while their role for germinal center ( GC ) formation is poorly understood. We found a dramatic reduction in the numbers of GC B cells when investigating different type 2 immune responses in IL ‐4/ IL ‐13‐deficient mice. IL ‐4/ IL ‐13 from T cells located outside B ‐cell follicles was sufficient for GC formation. We further revealed that IL ‐4/ IL ‐13 acts directly on B cells for the formation of a robust GC response. The frequency of apoptotic GC B cells was not altered in the absence of IL ‐4/ IL ‐13 and proliferation was even enhanced. However, deficiency of signal transducer and activator of transcription 6 signaling in B cells resulted in failure to downregulate the chemotactic receptor G pr183 ( E bi2) and downregulation of this receptor has been shown to be essential for proper GC B ‐cell differentiation. Thus, T ‐cell‐derived extrafollicular IL ‐4/ IL ‐13 and signal transducer and activator of transcription 6‐regulated genes in B cells play a critical role for orchestration of the GC response in type 2 immunity.