Objectives To predict the spread of coronavirus disease (COVID‐19), information regarding the immunological memory for disease‐specific antigens is necessary. The possibility of reinfection, as well as the efficacy of vaccines for COVID‐19 that are currently under development, will largely depend on the quality and longevity of immunological memory in patients. To elucidate the process of humoral immunity development, we analysed the generation of plasmablasts and virus receptor‐binding domain (RBD)‐specific memory B (Bmem) cells in patients during the acute phase of COVID‐19. Methods The frequencies of RBD‐binding plasmablasts and RBD‐specific antibody‐secreting cells (ASCs) in the peripheral blood samples collected from patients with COVID‐19 were measured using flow cytometry and the ELISpot assay. Results The acute phase of COVID‐19 was characterised by the transient appearance of total as well as RBD‐binding plasmablasts. ELISpot analysis indicated that most patients exhibited a spontaneous secretion of RBD‐specific ASCs in the circulation with good correlation between the IgG and IgM subsets. IL‐21/CD40L stimulation of purified B cells induced the activation and proliferation of Bmem cells, which led to the generation of plasmablast phenotypic cells as well as RBD‐specific ASCs. No correlation was observed between the frequency of Bmem cell‐derived and spontaneous ASCs, suggesting that the two types of ASCs were weakly associated with each other. Conclusion Our findings reveal that SARS‐CoV‐2‐specific Bmem cells are generated during the acute phase of COVID‐19. These findings can serve as a basis for further studies on the longevity of SARS‐CoV‐2‐specific B‐cell memory.
Immunoglobulin E (IgE) is the key immunoglobulin in the pathogenesis of IgE associated allergic diseases affecting 30% of the world population. Recent data suggest that allergen-specific IgE levels in serum of allergic patients are sustained by two different mechanisms: inducible IgE production through allergen exposure, and continuous IgE production occurring even in the absence of allergen stimulus that maintains IgE levels. This assumption is supported by two observations. First, allergen exposure induces transient increases of systemic IgE production. Second, reduction in IgE levels upon depletion of IgE from the blood of allergic patients using immunoapheresis is only temporary and IgE levels quickly return to pre-treatment levels even in the absence of allergen exposure. Though IgE production has been observed in the peripheral blood and locally in various human tissues (e.g., nose, lung, spleen, bone marrow), the origin and main sites of IgE production in humans remain unknown. Furthermore, IgE-producing cells in humans have yet to be fully characterized. Capturing IgE-producing cells is challenging not only because current staining technologies are inadequate, but also because the cells are rare, they are difficult to discriminate from cells bearing IgE bound to IgE-receptors, and plasma cells express little IgE on their surface. However, due to the central role in mediating both the early and late phases of allergy, free IgE, IgE-bearing effector cells and IgE-producing cells are important therapeutic targets. Here, we discuss current knowledge and unanswered questions regarding IgE production in allergic patients as well as possible therapeutic approaches targeting IgE.
The development of effective vaccines against SARS-CoV-2 remains a global health priority. Despite extensive use, the effects of Sputnik V on B cell immunity need to be explored in detail. We performed comprehensive profiling of humoral and B cell responses in a cohort of vaccinated subjects (n = 22), and demonstrate that Sputnik vaccination results in robust B cell immunity.We show that B memory cell (MBC) and antibody responses to Sputnik V were heavily dependent on whether the vaccinee had a history of SARS-CoV-2 infection or not. 85 days after the first dose of the vaccine, ex vivo stimulated MBCs from the vast majority of Sputnik V vaccinees produced antibodies that robustly neutralized the Wuhan Spike-pseudotyped lentivirus. MBC-derived antibodies from all previously infected and some of the naïve vaccine recipients could also cross-neutralize Beta (B.1.351) variant of SARS-CoV-2.Virus-neutralizing activity of MBC-derived antibodies correlated well with that of the serum antibodies, suggesting the interplay between the MBC and long-lived plasma cell responses. Thus, our in-depth analysis of MBC responses in Sputnik V vaccinees complements traditional serological approaches and may provide important outlook into future B cell responses upon re-encounter with the emerging variants of SARS-CoV-2.
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