Atypical B cells upregulate co-stimulatory molecules during malaria and secrete antibodies with T follicular helper cell support

Hopp, C. S.; Skinner, J.; Anzick, S. L.; Tipton, C. M.; Peterson, M. E.; Li, S.; Doumbo, S.; Kayentao, K.; Ongoiba, A.; Martens, C.; Traore, B.; Crompton, P. D.

doi:10.1101/2021.12.07.471601

bioRxiv · 10.1101/2021.12.07.471601

Atypical B cells upregulate co-stimulatory molecules during malaria and secrete antibodies with T follicular helper cell support

Hopp, C. S.·Skinner, J.·Anzick, S. L.·Tipton, C. M.·Peterson, M. E.·Li, S.·Doumbo, S.·Kayentao, K.·Ongoiba, A.·Martens, C.·Traore, B.·Crompton, P. D.

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Abstract

Several infectious and autoimmune diseases are associated with an expansion of CD21-CD27- atypical B cells (atBCs). The function of atBCs remains unclear and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal RNA-sequencing and flow cytometry analyses of Plasmodium falciparum (Pf)-specific B cells before and shortly after febrile malaria, with simultaneous analysis of influenza hemagglutinin (HA)-specific B cells as a comparator. B cell receptor-sequencing showed that Pf-specific atBCs, activated B cells (actBCs) and classical memory B cells share clonality and have comparable somatic hypermutation. In response to malaria, Pf-specific atBCs and actBCs expanded and upregulated molecules that mediate B-T cell interactions, suggesting that atBCs respond to T follicular helper (Tfh) cells. Indeed, in the presence of Tfh cells and Staphylococcal enterotoxin B, atBCs of malaria-exposed individuals differentiated into CD38+ antibody-secreting cells in vitro, suggesting that atBCs may actively contribute to humoral immunity to infectious pathogens. One Sentence SummaryThis study shows that atypical B cells actively respond to acute malaria and have the capacity to produce antibodies with T cell help.

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Hopp, C. S., Skinner, J., Anzick, S. L., Tipton, C. M., Peterson, M. E., Li, S., Doumbo, S., Kayentao, K., Ongoiba, A., Martens, C., Traore, B., Crompton, P. D.. 2021-12-07. Atypical B cells upregulate co-stimulatory molecules during malaria and secrete antibodies with T follicular helper cell support. https://doi.org/10.1101/2021.12.07.471601

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