Abstract
Abstract We have previously shown that C57BL/6J (B/6) peritoneal cavity (PerC) macrophages (Mfs), via IFNg-triggered iNOS expression, reduce T cell activation promoted by mitogens (ConA) or by TCR ligation (anti-CD3e, SEB, etc). We wanted to assess whether PerC B cells were also susceptible to this form of myeloid suppression. B/6 PerC B cell responses triggered by BCR {F(ab’)2 anti-IgM} and TLR4 (LPS/TLR4L) were both suppressed and could be liberated by blocking prostaglandin production with indomethacin; neutralization of IL10 also increased the LPS response. Suppression of the BALB/c (B/c) PerC B cell response to BCR ligation was similar but the TLR4 response was not suppressed. Where the addition of exogenous IL4 or IL13 suppressed the B/6 response to BCR ligation, IL4 increased this response in B/c mice. Most interestingly, the PerC B cell response to CD40 ligation was not suppressed in either strain and addition of IL10 increased this response; addition of IL4 or IL13 suppressed the B/6 response but had no impact upon B/c B cells. Concurrent CD40 and TCR ligation revealed that iNOS-mediated suppression overrides the B cell response. Considering that the high myeloid:lymphoid cell ratio found in PerC cell cultures mimics that seen in tumor microenvironments, these results serve to inform strategies designed to promote anti-cancer immunity.
Published Version
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