| Autor: |
Sharma, Rahul, Smolkin, Ryan M., Chowdhury, Priyanka, Fernandez, Keith Conrad, Kim, Youngjun, Cols, Montserrat, Alread, William, Yen, Wei-Feng, Hu, Wei, Wang, Zhong-Min, Violante, Sara, Chaligné, Ronan, Li, Ming O., Cross, Justin R., Chaudhuri, Jayanta |
| Zdroj: |
Nature Immunology; August 2023, Vol. 24 Issue: 8 p1358-1369, 12p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
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