ADAM17 is known to contribute to the immune system through its shedding of tumor necrosis factor alpha (TNF alpha). However, the role of ADAM17 in B cell biology is not well characterized. To determine whether B cell ADAM17 contributes to T cell-independent humoral immune responses, we crossed CD19 Cre transgenic mice with mice bearing a floxed allele of ADAM17 (ADAM17(CD)(19)). In this study, we show a B cell intrinsic role for ADAM17 in regulating marginal zone B cell (MZB) numbers in mice. Interestingly, we demonstrate that the loss of B cell ADAM17 results in reduced MZB numbers in the naive state and after immunization with T-independent antigen, yet enhanced humoral immunity to T cell independent antigens. We additionally find elevated TACI and CD138 levels on plasma cells following immunization in ADAM17(CD19) mice. Overall, these findings suggest that B cell ADAM17 may orchestrate T independent immune responses through both MZB numbers and plasma cell antibody production. (C) 2019 Elsevier Inc. All rights reserved.