Memory B‐cell diversity: From early generation to tissue residency and reactivation

Abstract

Memory B cells (MBCs) have a crucial function in providing an enhanced response to repeated infections. Upon antigen encounter, MBC can either rapidly differentiate to antibody secreting cells or enter germinal centers (GC) to further diversify and affinity mature. Understanding how and when MBC are formed, where they reside and how they select their fate upon reactivation has profound implications for designing strategies to improve targeted, next‐generation vaccines. Recent studies have crystallized much of our knowledge on MBC but also reported several surprising discoveries and gaps in our current understanding. Here, we review the latest advancements in the field and highlight current unknowns. In particular, we focus on timing and cues leading to MBC generation before and during the GC reaction, discuss how MBC become resident in mucosal tissues, and finally, provide an overview of factors shaping MBC fate‐decision upon reactivation in mucosal and lymphoid tissues.

Regulation of pulmonary plasma cell responses during secondary infection with influenza virus

“…Following primary infection with influenza virus, clusters of PCs that associate with iBALT-like structures develop and persist in the lung ( MacLean et al, 2022 ; Oh et al, 2021 ). Shortly after rechallenge, new PCs develop in these sites ( Allie and Randall, 2020 ; Chen and Laidlaw, 2022 ; Lee and Oh, 2022 ; Reusch and Angeletti, 2023 ), forming large aggregates that retain their confined distribution (referred in this study to as “clustered” PCs) ( MacLean et al, 2022 ) ( Fig. S1 A ).…”

Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses

“…We next defined the kinetics of relatedness-independent broadening of H1N1 HAI over the four year period by graphing the fraction of responders vs non-responders (detectable vs non detectable boosting of HAI to each H1N1 strain) at each year (Figure 3A-C). Although pandemic HA will not be historically imprinted, memory recall of pre-existing immunity or ‘back boosting’ to historical strains would occur in response to the first antigen exposure (Akkaya et al, 2020; Henry et al ., 2018; Nunez et al ., 2017; Palm and Henry, 2019; Reusch and Angeletti, 2023; Turner et al, 2020) and cannot be ruled out in the first vaccine year (2013). For this reason we focused on the initial non-responders, who boost against pHA (and the other seasonal vaccine components, see Figure 2B,C) but do not simultaneously broaden/back-boost against historical H1N1 strains after immunization in Year 1, and by definition lack B cell memory that is recalled by pHA (Figure 3A-C).…”

Reprogramming human B cells with custom heavy-chain antibodies

“…34,44 B cells also form memory cells, an antigen-responsive population that is at least as long-lived as plasma cells. 45 Memory B cells may play an important role in immune responses in tissues, including the lung mucosa and solid tumors, 46,47 and can also re-seed the plasma cell compartment in response to repeat antigen exposure. 48,49 The antigen-responsiveness of memory B cells could be exploited to support the amplification and persistence of engineered B cells, or to tune the levels of antibodies that are produced.…”