Phosphatidylcholine as a metabolic cue for determining B cell fate and function
In activated B cells, increased production of phosphatidylcholine (PtdCho), the most abundant cellular phospholipid, is handled primarily by the CDP-choline pathway. B cell-specific 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, suggesting that PtdCho synthesis is required for germinal center reactions. To specifically assess whether PtdCho influences B cell fate during germinal center responses, we examined immune responses in mice whereby PtdCho synthesis is disrupted in B cells that have undergone class switch recombination to IgG1 (referred to as either Cγ1, Cγ1 or Cγ1 based on Cre copy number). Serum IgG1 was markedly reduced in naïve Cγ1 and Cγ1 mice, while levels of IgM and other IgG subclasses were similar between Cγ1 and Cγ1 control mice. Serum IgG2b titers were notably reduced and IgG3 titers were increased in Cγ1 mice compared with controls. Following immunization with T cell-dependent antigen NP-KLH, control mice generated high titer IgG anti-NP while IgG anti-NP titers were markedly reduced in both immunized Cγ1 and Cγ1 mice. Correspondingly, the frequency of NP-specific IgG antibody-secreting cells was also reduced in spleens and bone marrow of Cγ1 and Cγ. 1 mice compared to control mice. Interestingly, though antigen-specific IgM B cells were comparable between Cγ1, Cγ1 and control mice, the frequency and number of IgG1 NP-specific B cells was reduced only in Cγ1 mice. These data indicate that PtdCho is required for the generation of both germinal center-derived B cells and antibody-secreting cells. Further, the reduction in class-switched ASC but not B cells in Cγ1 mice suggests that ASC have a greater demand for PtdCho compared to germinal center B cells.
Brewer, Joseph W.; Solodushko, Viktoriya; Aragon, Ileana; and Barrington, Robert A., "Phosphatidylcholine as a metabolic cue for determining B cell fate and function" (2016). Department of Microbiology and Immunology Faculty and Staff Publications and Presentations. 19.