Basics of memory B‐cell responses: lessons from and for the real world

Abstract

Summary The production of pathogen‐specific B cells and antibodies underlies protective immunity elicited by most vaccines and many infections. Humoral immunity follows a regulated process by which high‐affinity antibody‐secreting plasma cells and memory B cells are generated. Yet for certain pathogens, protective immunity is inefficiently generated and/or maintained. For example, Dengue virus infections lead to lasting immunity against re‐infection by the same serotype. However, if infected with a different Dengue serotype, the individual is predisposed to more severe disease than if he/she was completely naive. As another example, both natural infections with or vaccination against malaria do not necessarily lead to lasting immunity, as the same individual can be re‐infected many times over the course of a lifetime. In this review, we discuss how these real‐world problems can both instruct and be informed by recent basic studies using model organisms and antigens. An emphasis is placed on protective epitopes and functional distinctions between memory B‐cell subsets in both mice and humans. Using flavivirus and Plasmodium infections as examples, we also speculate on the differences between ineffective B‐cell responses that actually occur in the real world, and perfect‐world responses that would generate lasting immunity.

Single segment of spleen autotransplantation, after splenectomy for trauma, can restore splenic functions

“…Splenectomy has important consequences for the homeostasis of the immune system, and in particular, the B cell compartment seems to be the most involved. Our study confirmed the many observations regarding the impairment of B lymphocytes in these patients [16], showing that splenectomized patients (group B) have increased levels of B-naive and reduced levels of classswitched and unswitched memory B cells. In contrast, the autotransplanted patients did not present any significant differences for all of the evaluated B lymphocyte subsets compared to normal subjects.…”

“…The spleen is considered the site at which newly formed B lymphocytes are induced to mature into IgD recirculating B cells, the population that is able to initiate the humoral immune responses. In normal subjects, the B-naive cells rapidly recognize the antigen, proliferate and differentiate into short-lived plasma cells or germinal center B cells [16], thus contributing to T cell-dependent immune responses and leading to germinal center formation in follicles of secondary lymphoid organs. B cell interactions with follicular helper T cells represent a crucial step in the production of their memory B cell counterparts or plasma cells that produce high affinity, somatically mutated, class-switched antibodies [17].…”

Quantitative modeling of the effect of antigen dosage on B-cell affinity distributions in maturating germinal centers

“…Administering a recall Ag injection some time after vaccination generates responders Ab-secreting cells (Ab-SCs). These cells comprise both MCs, that can be stimulated to differentiate and produce Abs upon new Ag encounter ( McHeyzer-Williams et al, 2015 ; Dogan et al, 2009 ; Mesin et al, 2016 ; Inoue et al, 2018 ), and residual PCs formed during previous maturations; PCs belonging to the long-lived pool are capable of surviving up to a human lifetime in the absence of division ( Wong and Bhattacharya, 2019 ; Crotty et al, 2003 ). The affinity distribution of Ab-SCs is assumed to be a weighted mixture of the MC and PC populations, with fractions equal respectively to and , where the value of is expected to depend on the conditions under which the system is probed.…”

Antibody Responses to SARS-CoV-2: Let’s Stick to Known Knowns

“…LLPCs are the sources of this durable Ab production (41)(42)(43)(44)(45)(46). Humoral immunity to chronic infections such as those caused by HIV and human papillomavirus, where viral Ags can persist in the host, are more complex (47). Given the acute nature of SARS-CoV-2 infections, chronic infections will not be discussed further in this article.…”