Abstract
Germinal centers (GC) are sites for extensive B cell proliferation and homeostasis is maintained by programmed cell death. The complement regulatory protein Decay Accelerating Factor (DAF) blocks complement deposition on host cells and therefore also phagocytosis of cells. Here, we show that B cells downregulate DAF upon BCR engagement and that T cell-dependent stimuli preferentially led to activation of DAFlo B cells. Consistent with this, a majority of light and dark zone GC B cells were DAFlo and susceptible to complement-dependent phagocytosis, as compared with DAFhi GC B cells. We could also show that the DAFhi GC B cell subset had increased expression of the plasma cell marker Blimp-1. DAF expression was also modulated during B cell hematopoiesis in the human bone marrow. Collectively, our results reveal a novel role of DAF to pre-prime activated human B cells for phagocytosis prior to apoptosis.
Highlights
High affinity memory B cells and plasma cells (PCs) have undergone two distinct selection processes; during B cell development in the bone marrow [1] and during T cell-dependent germinal center (GC) responses in secondary lymphoid organs [2,3,4,5,6,7]
We found that CD59, CD35, and CD21 were expressed at similar levels regardless of zonal location or Decay Accelerating Factor (DAF) phenotype, we observed a trend of higher expression of CD35 and CD21 on DAFhi cells in both zones (Figure 4C)
We demonstrate that human Germinal centers (GC) B cells downregulate DAF on their cell surfaces, and that one function of this downregulation is to prime GC B cells for complement-dependent phagocytosis
Summary
High affinity memory B cells and plasma cells (PCs) have undergone two distinct selection processes; during B cell development in the bone marrow [1] and during T cell-dependent germinal center (GC) responses in secondary lymphoid organs [2,3,4,5,6,7]. The GC is traditionally divided into two zones based on their histological appearance where proliferation and somatic hypermutation occur in the dark zone (DZ) and T cell dependent selection in the light zone (LZ) [8]. Both the bone marrow and GCs are sites of extensive B cell proliferation. Without BCR engagement and co-stimulatory signals from CD4+ T cells, GC B cells undergo apoptosis and die. It has been suggested that human GC B cells are primed for apoptosis and phagocytosis [17], but a mechanism for this priming has not been demonstrated
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