CD6 is a novel positive regulator of natural antibody producing B-1a cells (INC1P.401)

Abstract

Abstract Although CD6 has recently been identified as a risk gene for multiple sclerosis, its biological function remains unclear, partially due to the lack of CD6 gene engineered animals. It is established that CD6 is present on all T cells in both humans and mice; however, it is believed that mouse B cells do not express CD6. B-1a B cells are the primary source of natural antibodies (Nabs), which provide the first line of defense against infection and facilitate the clearance of oxidized lipoproteins that contribute to the pathogenesis of atherosclerosis. By studying CD6 knockout (KO) and WT mice, we found that CD6 is basally expressed selectively on splenic B-1a B cells. CD6 KO mice exhibit smaller B1a B cell population in the spleen concomitant with lower titers of Nabs in the serum than those in WT mice. Interestingly, B-1a-cell-specified progenitors also express CD6 and the frequencies of these progenitors are significantly reduced in the CD6 KO mice. B cell receptor (BCR) signaling is critical for B1a B cell development and T-independent immunoglobulin response. CD6 KO B1a B cells displayed impaired BCR-induced JNK activation and elicited impaired T-independent antibody responses to NP-Ficoll. These findings suggest a positive role for CD6 in regulating B1a B cell homeostasis and immune response.