B cell repertoire and ageing.

A diverse B cell repertoire is essential for an effective immune response. Not only to provide a variety of antibodies to recognise the multiplicity of likely pathogen challenge, but also because B cells are important regulators of the immune response. In addition to their excellent capabilities as antigen presenting and activating cells, recent work shows that some subpopulations of B cells can have suppressive functions. The diversity of the B cell population as a whole decreases with age, and is associated with ill health. Whether decreased diversity is a feature of all B cells or a reflection of altered subpopulations is not clear, since different subsets of B cells have different functions and their repertoires are shaped by different selection pressures.

High-throughput immunoglobulin repertoire analysis distinguishes between human IgM memory and switched memory B-cell populations.

B-cell receptor (BCR) diversity is achieved centrally by rearrangement of Variable, Diversity, and Joining genes, and peripherally by somatic hypermutation and class-switching of the rearranged genes. Peripheral B-cell populations are subject to both negative and positive selection events in the course of their development that have the potential to shape the BCR repertoire. The origin of IgM(+)IgD(+)CD27(+) (IgM memory) cells is controversial. It has been suggested that they may be a prediversified, antigen-independent, population of cells or that they are a population of cells that develop in response to T-independent antigens. Most recently, it was suggested that the majority of IgM memory cells are directly related to switched memory cells and are early emigrants from the germinal center reaction. Advances in sequencing technology have enabled us to undertake large scale IGH repertoire analysis of transitional, naive, IgM memory and switched memory B-cell populations. We find that the memory B-cell repertoires differ from the transitional and naive repertoires, and that the IgM memory repertoire is distinct from that of class-switched memory. Thus we conclude that a large proportion of IgM memory cells develop in response to different stimuli than for class-switched memory cell development.