B cells promote CD8 T cell primary and memory responses to subunit vaccines

Abstract

SUMMARY The relationship between B cells and CD4 T cells has been carefully studied, revealing a collaborative effort in which B cells promote the activation, differentiation, and expansion of CD4 T cells while the so-called “helper” cells provide signals to B cells, influencing their class switching and fate. Interactions between B cells and CD8 T cells are not as well studied, although CD8 T cells exhibit an accelerated contraction after certain infections in B-cell-deficient mice. Here, we find that B cells significantly enhance primary CD8 T cell responses after vaccination. Moreover, memory CD8 numbers and function are impaired in B-cell-deficient animals, leading to increased susceptibility to bacterial challenge. We also show that interleukin-27 production by B cells contributes to their impact on primary, but not memory, CD8 responses. Better understanding of the interactions between CD8 T cells and B cells may aid in the design of more effective future vaccine strategies.

IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort

“…Marked elevation of IL-27 was reported in a single case of mRNA-1273 COVID-19 vaccine-related myocarditis, with more moderate increases in IL-27 in recently vaccinated control individuals (incidentally, inflammasome activation was also implicated in the vaccine-related myocarditis) ( 47 ). Indeed, IL-27 production by B cells has been shown to contribute to cytotoxic CD8 T cell responses to SARS-CoV-2 subunit vaccines, suggesting the importance of this cytokine in the viral response to SARS-CoV-2 ( 48 , 49 ). Additionally, blockade of IL-27 was reported to improve mortality in mouse models of endotoxin- and sepsis-induced cytokine storms ( 50 ).…”

Predictors for insufficient SARS-CoV-2 vaccination response upon treatment in multiple sclerosis

“… 19 Even though vaccination-specific CD4 and CD8 T cell induction in B cell depletion has been reported, lower levels were detected when vaccine-specific antibodies were lacking. 4 , 20 , 21 , 22 , 23 In contrast to this, two other studies report greater abundance of SARS-CoV-2 spike-specific and highly activated CD8 T cells in those B cell-depleted patients who were lacking spike antibodies. 4 , 11 These observations underline the complexity of the interconnection between B cell response and CD8 activation.…”

Single shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad and durable systemic and mucosal immune responses

“…Furthermore, Clec9A-RBD was able to elicit robust RBD-specific T cell memory that could be recalled 6-12 months post-immunization. IL-27 has been found to be critical for the formation and maintenance of memory T cells, whereby cDC1 and B cells were reported to be major producers of this cytokine [46-49]. Since the Clec9A-targeting approach facilitates interaction of T cells with cDC1, coupled with the persistence of RBD-specific B cells, these conditions likely favor IL-27-mediated signaling, thereby promoting induction and maintenance of memory T cells.…”