Phosphatidylcholine as a metabolic cue for determining B cell fate and function (LYM6P.774)

Abstract

Abstract In activated B cells, increased production of phosphatidylcholine (PtdCho), the most abundant cellular phospholipid, is handled primarily by the CDP-choline pathway. Previous studies revealed that CD19Cre-mediated deletion of CTP:phosphocholine cytidylyltransferase α (CCTα), the rate-limiting enzyme in the CDP-choline pathway, led to augmented IgM secretion and reduced IgG production, consistent with defective germinal center reactions. To more specifically assess the influence of PtdCho on B cell fate during germinal center and long-term humoral responses, we examined immune responses in Cγ1Cre CCTαflox mice. Serum IgG1 was undetectable in naïve Cγ1Cre CCTαflox mice, while levels of IgM and other IgG subclasses were similar in naïve Cγ1Cre CCTαflox and control mice. Following immunization with T cell-dependent antigen NP-KLH, control mice predictively generated high titer IgG anti-NP. In contrast, IgG anti-NP titers were markedly reduced in immunized Cγ1Cre CCTαflox mice. Interestingly, though antigen-specific IgM responses were comparable between Cγ1Cre CCTαflox and control mice, the IgM anti-NP response in Cγ1Cre CCTαflox mice failed to increase in affinity. Lastly, the frequency of antigen-experienced NP-specific B cells and antibody-secreting cells (ASC) were both reduced in Cγ1Cre CCTαflox mice compared with controls. These data indicate that PtdCho plays a pivotal role in the generation and persistence of both germinal center B cells and ASC.