Molecular programming of B cell memory

Abstract

The development of high-affinity B cell memory is regulated through three separable phases, each involving antigen recognition by specific B cells and cognate T helper cells. Initially, antigen-primed B cells require cognate T cell help to gain entry into the germinal centre pathway to memory. Once in the germinal centre, B cells with variant B cell receptors must access antigens and present them to germinal centre T helper cells to enter long-lived memory B cell compartments. Following antigen recall, memory B cells require T cell help to proliferate and differentiate into plasma cells. A recent surge of information — resulting from dynamic B cell imaging in vivo and the elucidation of T follicular helper cell programmes — has reshaped the conceptual landscape surrounding the generation of memory B cells. In this Review, we integrate this new information about each phase of antigen-specific B cell development to describe the newly unravelled molecular dynamics of memory B cell programming.

Lyn Signaling To Upregulate GANP Is Critical for the Survival of High-Affinity B Cells in Germinal Centers of Lymphoid Organs

“…Upon immunization with soluble Ag, naive Ag-reactive B cells proliferated rapidly in the dark zone and then differentiated in the light zone of the GCs undergoing the maturation process to express high-affinity and class-switched BCRs. The GC reaction presumably occurs through multiple-round processes during the immune response, remaining as mGC B cells to gain better affinity or alternatively differentiating into long-lived plasma cells in the spleen that later appear in the bone marrow (25). The ASCs reactive to the Ag with a low amount of NP are estimated to produce high-affinity anti-NP Ab of the IgG 1 isotype.…”

IFN-γ–Producing CD4+ T Cells Promote Generation of Protective Germinal Center–Derived IgM+ B Cell Memory against Salmonella Typhi

“…2B), which could represent long-lived plasma cells that can contribute to the maintenance of high serum titers (43). Alternatively, IgM B cell memory and high serum Ab titers can be maintained by a CD4 + T cell-dependent GC reaction (25,26). To dissect the contribution of CD4 + T cells in the anti-porin IgM responses, MHC class II-deficient mice (Iab 2/2 ), which lack CD4 + T cells but maintain a normal CD8 T cell compartment (44), were immunized in a prime/boost regimen and B cell responses against porins were evaluated.…”

“…The major functions of the GC reaction are Ab diversification through class-switch recombination and the generation of affinity-matured B cells through the process of somatic hypermutation (25). Moreover, GCs facilitate the generation of B cell memory and produce large numbers of short-and long-lived plasma cells that provide high Ab titers in serum (26).…”

“…For example, maintenance of protective B cell responses against viruses hiding in distinct sanctuaries depends on the continued support from CD4 + T cells (30,31). The GC reaction that generates such B cell responses is regulated by a specific CD4 + T cell type known as T follicular helper (Tfh) cells, which can differentiate into various subtypes (e.g., Th1-like, Th2-like, Th17-like) (25,32). Tfh cell differentiation is initiated through contact with Ag-expressing dendritic cells (DCs) (33), leading to the rapid induction of the Tfh signature transcription factor BCL-6 (34).…”

Mechanisms of action of BCL6 during germinal center B cell development

“…Next, antigen-engaged B-cells migrate to the border between the follicles and the T cell zone or interfollicular zones, where they undergo proliferation and interact with cognate Tfh cells within 1-3 days after stimulation [18][19][20][21]. B-cells can then differentiate into extrafollicular plasma cells and leave the follicle to generate low-affinity antibodies, or alternatively can enter the GC pathway [22]. These early GC precursor B cells (i.e.…”