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Regulation of Decay Accelerating Factor primes human germinal center B cells for phagocytosis

ABSTRACT: Germinal centers (GCs) are structures in secondary lymphoid organs, essential for an efficient humoral immune response. Complement interaction with B cells facilitates B cell activation, but little is known about the role of complement regulators during B cell activation and differentiation. By flow cytometric analysis, we could show that the majority of human GC B cells had decreased expression of the negative complement regulator Decay Accelerating Factor (DAF). Transcriptomic analysis revealed that DAFlo GC B cells upregulated genes associated with gene editing and proliferation, whereas DAFhi GC B cells had increased expression of genes involved in cell differentiation. We could confirm that DAFhi GC B cells expressed the transcription factor Blimp1 on protein level, which indicates that DAFhi GC B cells may be early plasmablasts/plasma cells. Then, we assessed the expression of the complement regulator CD59, which inhibits the membrane attack complex that lyses cells. We found that the expression was low in naïve and memory B cells, but increased in GC and plasmablasts/plasma cells. This suggests that DAFlo GC B cells may be primed for phagocytosis rather than lysis. By cell sorting, we could show that DAFlo GC B cells were phagocytosed to a greater extent than DAFhi GC B cells, both in presence and absence of complement. Stimulation of the B cell receptor on circulating B cells induced DAFlo cells. Finally, we also identified specific downregulation of DAF during early B cell development in the human bone marrow. As a conclusion, we suggest that complement regulators serve specific functions at stages of B cell selection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153741 | GEO | 2020/12/31

REPOSITORIES: GEO

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