Abstract
Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact. A focused transcriptome analysis at single cell level allowed the dissection of the CD8 positive B cell population. We found that the affected cells are characteristically of the CD27+CD200- phenotype, and consist of two discrete late-stage subpopulations that carry signatures of activated memory B like cells, and early plasmablasts. Thus, there is only a restricted time window in the differentiation process during which B cells can intimately interact with CD8+ T cells. The findings point to a novel link between the T and B arms of the adaptive immune system, and suggest that CD8+ T cells have the capability to directly shape the global antibody repertoire.
Highlights
Upon antigen encounter, naive B cells undergo a strictly controlled maturation and selection process before they eventually turn into plasma cells with high antibody secretion capabilities
Most of the crucial steps occur in germinal centers (GCs) of secondary lymphoid organs (reviewed in [1,2], where their fate is primarily determined by interactions with two cell types, (a) follicular dendritic cells (FDCs), which serve as antigen reservoir and are the major antigen presenting cells starting the affinity maturation process, and (b) germinal center T cells, that provide cognate help to B cells, mainly via the CD40-CD40L pathway
It was rather surprising that we have repeatedly detected CD8 molecules on the surface of a small subset of B cells in GCSF mobilized apheresis material: so far in every examined apheresis sample up to 2% of the B cells were CD8 positive
Summary
Naive B cells undergo a strictly controlled maturation and selection process before they eventually turn into plasma cells with high antibody secretion capabilities. Most of the crucial steps occur in germinal centers (GCs) of secondary lymphoid organs (reviewed in [1,2], where their fate is primarily determined by interactions with two cell types, (a) follicular dendritic cells (FDCs), which serve as antigen reservoir and are the major antigen presenting cells starting the affinity maturation process, and (b) germinal center T cells, that provide cognate help to B cells, mainly via the CD40-CD40L pathway. A third type of cells, CD4+ T follicular helper cells (TFHs) are required to complete the differentiation of B cells, and to instruct them to leave to GC area [3]. Contribution of other GC associated cells, in particular CD8+ T cells, to B cell differentiation remains largely unmapped.
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