| First Author | Brewer JW | Year | 2016 |
| Journal | Cell Immunol | Volume | 310 |
| Pages | 78-88 | PubMed ID | 27502364 |
| Mgi Jnum | J:346367 | Mgi Id | MGI:6869312 |
| Doi | 10.1016/j.cellimm.2016.08.002 | Citation | Brewer JW, et al. (2016) Phosphatidylcholine as a metabolic cue for determining B cell fate and function. Cell Immunol 310:78-88 |
| abstractText | 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 alpha (CCTalpha), 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 Cgamma1(wt/wt), Cgamma1(Cre/wt) or Cgamma1(Cre/Cre) based on Cre copy number). Serum IgG1 was markedly reduced in naive Cgamma1(Cre/wt) and Cgamma1(Cre/Cre) mice, while levels of IgM and other IgG subclasses were similar between Cgamma1(Cre/wt) and Cgamma1(wt/wt) control mice. Serum IgG2b titers were notably reduced and IgG3 titers were increased in Cgamma1(Cre/Cre) 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 Cgamma1(Cre/wt) and Cgamma1(Cre/Cre) mice. Correspondingly, the frequency of NP-specific IgG antibody-secreting cells was also reduced in spleens and bone marrow of Cgamma1(Cre/wt) and Cgamma. 1(Cre/Cre) mice compared to control mice. Interestingly, though antigen-specific IgM B cells were comparable between Cgamma1(Cre/wt), Cgamma1(Cre/Cre) and control mice, the frequency and number of IgG1 NP-specific B cells was reduced only in Cgamma1(Cre/Cre) 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 Cgamma1(Cre/wt) mice suggests that ASC have a greater demand for PtdCho compared to germinal center B cells. |
