Principal Investigator

David Topham, Ph.D. University of Rochester work Box 609 601 Elmwood Ave Rochester NY 14642 office: KMRB 3-9631 p 585-273-1403 f 585-273-2452

B-Cell Response to Viruses that Infect the Respiratory Tract (M. Sangster)

An electron micrograph of a section of lung tissue infected with influenza virus 14 days previously. The image shows the presence of an antibody secreting B cell located in the airway. This may be one of the B cells that is making antibodies which protect from influenza infection. The wavy lines that surround the nucleus of the cell (demarcated by the letter B) are layers of endoplasmic reticulum where the antibody proteins are synthesized by the B cell for secretion into the surrounding tissue.

Virus-specific antibodies play a key role in providing a protective barrier to infection and in facilitating viral clearance once an infection is established. Antibody-producing cells or plasma cells are generated from B cells that divide and differentiate following recognition of specific antigen. A critical requirement for optimal antibody responses is the cognate help delivered to activated B cells by CD4 T cells. This help is important for directing antibody isotype switching in B cells, the process by which B cells switch from expressing IgM to expressing alternative isotypes (such as IgG1, IgG2a, and IgA in the mouse) with different functional characteristics. In addition, cognate T cell help is critical if activated B cells are to participate in germinal center reactions, where affinity maturation of the antibody response takes place and the cellular elements of B cell memory are generated.

These elements include long-lived plasma cells, which maintain high levels of protective antibodies, and a population of memory B cells that will respond with rapid antibody production on re-exposure to cognate antigen. This brief overview grossly simplifies a remarkable and complex process that is regulated at many levels in ways that modulate the kinetics, magnitude, and quality of the acute B cell response, as well as characteristics of dispersed plasma cell and memory B cell populations. In general terms, our research is aimed at understanding the characteristics of optimally effective B cell responses and applying this knowledge towards the improvement of vaccination regimens.

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