Vaccination-induced changes in human B-cell repertoire and pneumococcal IgM and IgA antibody at different ages.

It is well known that older people are more susceptible to morbidity and mortality from infectious diseases, particularly from pulmonary diseases such as pneumococcal pneumonia where vaccines do not provide efficient protection as in younger populations. We have previously shown that the B-cell repertoire in the old is reduced and hypothesise that this may contribute to the impaired humoral responses of the elderly. Here, we investigated the repertoire and antibody responses to winter vaccination in two age groups, aged 18-49 and 65-89.

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.

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.

The ageing B cell population: composition and function.

Age-related changes in the structure and function of the immune system, collectively termed immunosenescence, result in poor responses to infections, increased susceptibility to cancers and increased incidence of autoimmune diseases. The humoral immune response, maintained by the B cell compartment, has a key role in an effective immune system-not only in producing high affinity antibodies that are crucial for vaccination strategies, but in assisting other components of the immune system in their function. Hence an understanding of B cell immunosenescence in particular is vital in designing strategies to combat the effects of age on immune function.

Regulation of B-cell differentiation by microRNAs and RNA-binding proteins.

Post-transcriptional control of gene expression is an important mechanism for maintaining cellular homoeostasis and regulating the immune response to infection. It allows control of mRNA abundance, translation and localization. Mechanisms for post-transcriptional control involve RNA-binding proteins and miRNAs (microRNAs).