Distinct metabolic requirements regulate B cell activation and germinal center responses Journal Article
| Authors: | Sharma, R.; Smolkin, R. M.; Chowdhury, P.; Fernandez, K. C.; Kim, Y.; Cols, M.; Alread, W.; Yen, W. F.; Hu, W.; Wang, Z. M.; Violante, S.; Chaligné, R.; Li, M. O.; Cross, J. R.; Chaudhuri, J. |
| Article Title: | Distinct metabolic requirements regulate B cell activation and germinal center responses |
| Abstract: | Following infection or vaccination, activated B cells at extrafollicular sites or within germinal centers (GCs) undergo vigorous clonal proliferation. Proliferating lymphocytes have been shown to undertake lactate dehydrogenase A (LDHA)-dependent aerobic glycolysis; however, the specific role of this metabolic pathway in a B cell transitioning from a naïve to a highly proliferative, activated state remains poorly defined. Here, we deleted LDHA in a stage-specific and cell-specific manner. We find that ablation of LDHA in a naïve B cell did not profoundly affect its ability to undergo a bacterial lipopolysaccharide-induced extrafollicular B cell response. On the other hand, LDHA-deleted naïve B cells had a severe defect in their capacities to form GCs and mount GC-dependent antibody responses. In addition, loss of LDHA in T cells severely compromised B cell-dependent immune responses. Strikingly, when LDHA was deleted in activated, as opposed to naïve, B cells, there were only minimal effects on the GC reaction and in the generation of high-affinity antibodies. These findings strongly suggest that naïve and activated B cells have distinct metabolic requirements that are further regulated by niche and cellular interactions. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | controlled study; gene deletion; nonhuman; lymphocyte proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animal experiment; b lymphocyte; b-lymphocytes; germinal center; lymphocyte activation; cellular immunity; antibody response; cell communication; cell metabolism; antibody affinity; b lymphocyte activation; bacterium lipopolysaccharide; aerobic glycolysis; article; lactate dehydrogenase a |
| Journal Title: | Nature Immunology |
| Volume: | 24 |
| Issue: | 8 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-08-01 |
| Start Page: | 1358 |
| End Page: | 1369 |
| Language: | English |
| DOI: | 10.1038/s41590-023-01540-y |
| PUBMED: | 37365386 |
| PROVIDER: | scopus |
| PMCID: | PMC11262065 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Jayanta Chaudhuri -- Source: Scopus |
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