In vivo regulation of autoreactive B cells by IL-6, CD40L and TNFα

In vivo regulation of autoreactive B cells by IL-6, CD40L and TNFα Public Deposited

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Creator

Wagner, Nikki J.
- Affiliation: School of Medicine, Department of Microbiology and Immunology

Abstract

Polyclonal B cell activation is essential to an effective innate immune response. However, autoreactive B cells must not be included in the polyclonal response to avoid autoimmunity. We have shown that IL-6 and CD40L secreted by TLR-stimulated dendritic cells (DCs) and macrophages (MΦs) selectively repress LPS-induced Ig secretion by autoreactive B cells. Here we introduce a third soluble factor involved in DC/MΦ-mediated B cell repression, TNFα. Like IL-6 and CD40L, DCs and MΦs derived from lupus-prone MRL/lpr mice secrete less TNFα in response to TLR stimulation than DCs and MΦs from C57BL/6 mice, suggesting secretion of TNFα by DCs/MΦs may have a role in autoimmune disease. We further demonstrate in an in vivo model that IL-6, CD40L and TNFα regulate LPS-stimulated autoreactive B cells, while mice lacking these factors do not. Our data indicate that IL-6, CD40L and TNFα mediate in vitro and in vivo autoreactive B cell repression during innate immune responses.

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