Journal of Clinical and Cellular Immunology
Open Access

Role of Memory B cells in response to flavivirus infections

Olivia Dubois^{* *}Correspondence: Olivia Dubois, Department of Immunology, Fudan University, Shanghai, China, Email:

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Description

Memory B Cells (MBCs) play an essential role in the immune response by either responding to previously encountered pathogens or by adapting their specificity when exposed to new antigens. These cells are capable of producing long-lasting immunity by either selecting preexisting clones or by generating new, refined specificities through the formation of secondary Germinal Centers (GCs). This study investigates the mechanisms through which MBCs respond to heterologous flavivirus infections, such as West Nile, Japanese encephalitis, Zika and dengue viruses, with a focus on their responses to the envelope protein Domain III (DIII).

Upon reexposure to an antigen, MBCs can react in two primary ways: they can either select preexisting clones from the diverse repertoire of antigen-specific cells or initiate new rounds of affinity maturation through secondary GCs. However, the specific mechanisms involved can differ depending on factors such as the nature of the original infection, the heterologous challenge and the antigenic properties of the pathogen. In this study, researchers examined the recall responses of MBCs after the challenge of different flaviviruses, utilizing a conditional deletion model of Activation-Induced cytidine Deaminase (AID), an enzyme essential for class-switch recombination and affinity maturation.

The results indicated that the recall response to flavivirus antigens was largely unaffected by the deletion of AID. This suggests that MBCs are primarily selecting preexisting clones, rather than undergoing extensive secondary GC reactions or further affinity maturation, in response to heterologous flavivirus challenges. Moreover, MBCs specific to DIII were predominantly found within a plasma-cell-biased subset expressing CD80, a marker typically associated with the differentiation of memory cells into antibody-producing plasma cells. This observation further supports the conclusion that the recall response in flavivirus infections involves the clonal selection of existing MBCs, rather than the generation of new B cell clones through secondary GCs.

One significant finding of the study was the identification of lowaffinity antigen-specific MBCs, which appeared to be preferentially selected for the recall response. This suggests that the diversity of the MBC compartment is maintained by the selection of these relatively low-affinity B cells, which may help to preserve the ability of the immune system to recognize a broad range of potential antigenic variations, such as those arising from antigenically distinct or mutated viruses.

The study further demonstrated the role of antigenic diversity in the MBC compartment. In the context of flavivirus infections, which include a wide variety of antigenically related but distinct viruses, the diversity of MBCs allows for the recognition of epitopes that may be conserved across different virus strains. This diversity may be important for combating viral escape mutants or heterologous viruses that may evade preexisting antibody-mediated immunity. However, the recall response to heterologous flaviviruses did not result in the generation of new GCs, implying that the immune system relies on the preexisting clonal repertoire rather than refining it further through additional rounds of affinity maturation.

These findings have important implications for the design of flavivirus vaccines. The ability of MBCs to respond to heterologous viruses through the clonal selection of preexisting diversity suggests that the immune system does not always require new rounds of GC responses to generate protective immunity. Instead, the key to a successful recall response may lie in harnessing the diversity of the existing MBC repertoire. By designing immunogens that promote a more focused MBC response, it may be possible to avoid the potential risks associated with infection enhancement, a phenomenon where antibodies generated against one virus strain exacerbate infection with a related strain.

Conclusion

Overall, the results of this study contribute to a better understanding of how MBCs respond to heterologous infections and immunizations. They suggest that MBCs can efficiently provide immunity against flaviviruses by selecting from a diverse pool of preexisting clones, without the need for extensive secondary GC reactions or affinity maturation. This knowledge could inform the development of vaccines that harness the natural diversity of the MBC compartment, potentially reducing the risk of antibody-dependent enhancement and improving the efficacy of vaccines against complex pathogens like flaviviruses.