Abstract
Vaccine-induced immunity depends on the generation of memory B cells (MBC). However, where and how MBCs are reactivated to make neutralising antibodies remain unknown. Here we show that MBCs are prepositioned in a subcapsular niche in lymph nodes where, upon reactivation by antigen, they rapidly proliferate and differentiate into antibody-secreting plasma cells in the subcapsular proliferative foci (SPF). This novel structure is enriched for signals provided by T follicular helper cells and antigen-presenting subcapsular sinus macrophages. Compared with contemporaneous secondary germinal centres, SPF have distinct single-cell molecular signature, cell migration pattern and plasma cell output. Moreover, SPF are found both in human and mouse lymph nodes, suggesting that they are conserved throughout mammalian evolution. Our data thus reveal that SPF is a seat of immunological memory that may be exploited to rapidly mobilise secondary antibody responses and improve vaccine efficacy.
Highlights
Vaccine-induced immunity depends on the generation of memory B cells (MBC)
To determine the immune response pathways involved in MBC reactivation, we adoptively transferred SWHEL B cells[16] expressing the optical highlighter Kaede[17] and OT2 T cells[18], and immunised recipient mice with the cognate antigen hen egg lysozyme (HEL) conjugated to ovalbumin (OVA)
MBCs are able to survive independent of antigen-derived BCR signals[19] and T cell help[20,21], unlike germinal centre (GC) B cells which are dependent on both[22,23]
Summary
Vaccine-induced immunity depends on the generation of memory B cells (MBC). where and how MBCs are reactivated to make neutralising antibodies remain unknown. We show that MBCs are prepositioned in a subcapsular niche in lymph nodes where, upon reactivation by antigen, they rapidly proliferate and differentiate into antibody-secreting plasma cells in the subcapsular proliferative foci (SPF) This novel structure is enriched for signals provided by T follicular helper cells and antigen-presenting subcapsular sinus macrophages. Vaccines have been empirically developed to harness this power of the immune system to remember past exposures to infectious organisms, and humoral immunity against common viral and vaccine antigens have been shown to provide life-long protection against reinfection[1] This protection is mediated by neutralising antibodies secreted by long-lived plasma cells (LLPCs) and by memory B cells (MBCs) that proliferate and differentiate more rapidly than naive B cells into antibody-secreting plasma cells upon re-exposure to the antigen[2]. We describe similar microanatomical structures in lymph nodes from patients, demonstrating that this is an evolutionarily conserved immune response pathway
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