Role of KLFs in B-cell differentiation and activation. In response to activation of the BCR, FOXO transcription factors target KLF4 which, on overexpression, inhibits B-cell proliferation and promotes G₁ cell-growth arrest. Conversely, B cell–specific, KLF4-deficient mice have displayed modest differentiation defects of pre-B cells in bone marrow and mature B cells in spleen; however, no differences were observed in these types of B cells using a similar conditional knockout model.⁸⁴  KLF4 or KLF9 overexpression reduces the number of proliferating memory B cells, and their behavior resembles that of naive B cells. In contrast, KLF2 increases the survival of anti-IgM and anti–CD40-stimulated memory B cells.