Impact of cytomegalovirus infection on B cell differentiation and cytokine production in multiple sclerosis

Zabalza, Ana; Vera, Andrea; Alari-Pahissa, Elisenda; Munteis Olivas, Elvira; Moreira Villanueva, Antía; Yélamos López, José; Llop, Mireia; López-Botet, M. (Miguel); Martínez Rodríguez, José Enrique

doi:http://dx.doi.org/10.1186/s12974-020-01840-2

Impact of cytomegalovirus infection on B cell differentiation and cytokine production in multiple sclerosis

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Zabalza A, Vera A, Alari-Pahissa E, Munteis E, Moreira A, Yélamos J, Llop M, López-Botet M, Martínez-Rodríguez JE. Impact of cytomegalovirus infection on B cell differentiation and cytokine production in multiple sclerosis. J Neuroinflammation. 2020; 17(1):161. DOI: 10.1186/s12974-020-01840-2

Abstract

Background: Human cytomegalovirus (HCMV) infection has been recently associated with a low risk of multiple sclerosis (MS), yet the basis behind this observation remains uncertain. In this study, we aimed to determine in MS patients whether HCMV induces modifications in the peripheral B cell compartment. Methods: HCMV serostatus was determined in 73 MS patients (55 relapsing-remitting MS (RRMS); 18 progressive MS (PMS)) and 30 healthy controls, assessing their B cell immunophenotype and cytokine production (GM-CSF, IL-6, IL-10, and TNFα) by flow cytometry. Results: HCMV seropositivity in untreated MS patients (n = 45) was associated with reduced switched memory B cells, contrasting with an opposite effect in PMS. Expansions of transitional B cells were observed in HCMV(+) IFNβ-treated RRMS patients but not in HCMV(-) cases (p < 0.01), suggesting that HCMV may influence the distribution of B cell subsets modulating the effects of IFNβ. Considering the B cell functional profile, HCMV(-) PMS displayed an increased secretion of proinflammatory cytokines (IL-6, TNFα) as compared to HCMV(+) PMS and RRMS cases (p < 0.001). Conclusions: Our study reveals an influence of HCMV infection on the phenotype and function of B cells, promoting early differentiation stages in RRMS and reducing the proinflammatory cytokine profile in advanced MS forms, which might be related with the putative protective role of this virus in MS.