Phänotypische, genetische und funktionelle Charakterisierung humaner Gedächtnis-B-Zell-Subpopulationen

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Traditionally, IgM+IgD+ B cells were considered as naive B cells and class-switched cells as memory B cells. We described two IgM-expressing B cell subsets (IgM+IgD- (IgM-only) and IgM+IgD+CD27+ B cells) that also carry mutated V genes. It is controversely discussed whether these cells are germinal centre (GC)-derived memory B cells, they derive from T cell-independent immune responses or they are generated in an antigen-independent primary diversification process. We aim to clarify the origin and functions of the two mutated IgM-expressing B cell subsets. In the first part of the project, we showed that the mutated IgM+ B cells are phenotypically more similar to class-switched memory than to naïve B cells and that IgM+ B cells are not undergoing somatic hypermutation in the marginal zone. We began with a genechip analysis of the B cell subsets. First indication was obtained that IgM+IgD+ GC B cells may be the origin of the mutated IgM+ B cells. In the present proposal we plan to a) study differential gene expression of the four main B cell subsets to reveal the origin and specific functions of the mutated IgM+ B cells, b) perform in vitro studies with the B cell subsets to characterise their specific functions, c) analyse the mutated IgM+ B cells for mutations in the Bcl-6 gene as a molcular trait of a GC derivation, d) continue the molecular analysis of IgM+IgD+ GC B cells, and e) perform a molecular characterization of an unusal population of “IgD-only” B cells.