Marginal zone B-cells, a gatekeeper of innate immunity

Abstract

To maintain the integrity of an organism constantly challenged by pathogens, the immune system is endowed with a variety of cell types. B lymphocytes were initially thought to only play a role in the adaptive branch of immunity. However, a number of converging observations revealed that two B-cell subsets, marginal zone (MZ) and B1 cells, exhibit unique developmental and functional characteristics, and can contribute to innate immune responses. In addition to their capacity to mount a local antibody response against type-2T-cell-independent (TI-2) antigens, MZ B-cells can participate toT-cell-dependent (TD) immune responses through the capture and import of blood-borne antigens to follicular areas of the spleen. Here, we discuss the multiple roles of MZ B-cells in humans, non-human primates, and rodents. We also summarize studies -performed in transgenic mice expressing fully human antibodies on their B-cells and in macaques whose infection with Simian immunod-eficiency virus (SIV) represents a suitable model for HIV-1 infection in humans -showing that infectious agents have developed strategies to subvert MZ B-cell functions. In these two experimental models, we observed that two microbial superantigens for B-cells (pro-tein A from Staphylococcus aureus and protein L from Peptostreptococcus magnus)as well as inactivated AT-2 virions of HIV-1 and infectious SIV preferentially deplete innate-like B-cells -MZ B-cells and/or B1 B-cells -with different consequences on TI and TD anti-body responses. These data revealed that viruses and bacteria have developed strategies to deplete innate-like B-cells during the acute phase of infection and to impair the anti-body response. Unraveling the intimate mechanisms responsible for targeting MZ B-cells in humans will be important for understanding disease pathogenesis and for designing novel vaccine strategies. © 2011 Zouali and Richard.