Neutrophils and marginal zone B cells – a new partnership

Being interconnected – that’s one of cardinal features pertinent to the mammalian immune system. Cellular subsets involved in an immune response seldom act alone beyond the initial signal recognition stage. Instead, the converging and augmentation of warning signs, the induction, adjustments or limitations of effector branches and finally the maintenance of immunological memory – these steps are usually carried out by two or more interacting populations. It is always so interesting to learn about new connections between cells of immune system, therefore recent report describing the supportive role of neutrophils in the antibody secretion process has immediately caught my attention.

The link to the publication:

http://www.nature.com/ni/journal/v13/n2/abs/ni.2194.html

This article reminds me the other, now pretty notorious story about the partnership of germinal center B cells and follicular helper CD4 T cells – an interaction that’s been proven to be so important during the antibody maturation process. But we have quite other players this time around.  Marginal zone B cells form the population posed at the anatomical intersection between circulation and lymphoid areas in the spleen. They are considered to possess blood filtering functions and are critically important in sepsis. There also were reports describing their pre-activated phenotype, which means that they can be easily stimulated to make antibodies. Neutrophils are most numerous granulocytes; they are cells extremely proficient in phagocytosis – kind of the always-ready emergency crew generally thought to be the first line of defense.

The research is performed on human cells combining imaging and functional data. The paper starts with series of pictures showing that neutrophils can colonize the splenic marginal zone under homeostatic but not inflammatory conditions. As a control authors perform the identical staining procedure with secondary lymphoid organs that have no marginal zone like tonsils, Peyer’s patches and peripheral lymph nodes. Then, compelling and diverse evidences are presented on how neutrophils enhance repertoire diversification and antibody secretion by marginal zone B cells. Apart from that, authors provide an in-depth description of the novel neutrophil “B helper” phenotype that is attained on contact with splenic epithelial cells.

However, it is the last and shortest paragraph of result section that really draws my attention. According to authors the increase in splenic colonization by neutrophils correlates with postnatal microbial colonization and fluorescence microscopy has shown LPS presence in adult but not fetal spleens. LPS was also shown to boost reprogramming of neutrophils to the “B helper” phenotype by splenic epithelial cells. Additionally, germ-free mice displayed lower levels of “B helper” neutrophils. Authors state – “Thus, we propose that TLR signals from mucosal commensals enhanced the splenic recruitment and reprogramming of N BH cells to enhance innate MZ B cell responses to highly conserved microbial TI antigens”.

Postnatal microbial colonization is the process of inhabiting intestines by commensal bacteria known as microbiota. It occurs soon after birth and has the instructive as well as regulatory effect on our immune system. Obviously the innate arm of immunity has the ability to detect microbial products and convey signals to start the inflammation. However, under normal circumstances the presence of microbiota is accommodated, although how exactly it happens is not entirely clear. Before I’ve read this paper I thought that so called microbial translocation or in other words the leakage of bacterial material from intestines into the bloodstream could happen exclusively as a pathological process.  Our body needs to be kept sterile; otherwise fatal disaster like sepsis may develop. So how to explain LPS presence in the spleen detected under homeostatic, non-inflammatory conditions? The most intuitive answer would be that the low-level trickling of unwanted bacterial stuff from the gut is taking place on the normal basis. Hence neutrophils may be assigned the duty of “garbage workers”, especially around big lymphoid organs like spleen.

I wish that somebody confirmed the neutrophils/marginal zone B cells partnership in murine models that may allow manipulation with relevant genetic backgrounds and cellular populations. The obvious problem to be solved is what will happen when there are no “B helper” neutrophils around. Will that impair the ability of marginal zone B cells to mount the effective protection against blood-borne antigens? However, it is not the only question I would ask. Authors present data showing that “B helper” neutrophils are able to contain CD4 T cells’ proliferation, although they never really explore this feature. May their function be more inhibitory than stimulatory? Somehow, that unexpected LPS presence in spleen keeps on intriguing me.  But now I have no idea how to interpret that.

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