Richard Riley, Ph.D.
Professor of Microbiology & Immunology
Description of Research
Altered B Cell Development in Senescence. Senescent mice show diminished B lymphopoiesis when compared to young mice and typically exhibit decreased numbers of pre-B cells and newly formed B cells within the bone marrow. Dr. Riley’s laboratory has focused upon elucidating the mechanisms responsible for the altered B lymphopoiesis in old age and also the ramifications for antibody repertoire and humoral immunity. In particular, they have found that B lymphopoiesis in old age is partially interrupted at the pro-B to pre-B cell transition, a developmental step which requires both function of the pre-B cell receptor complex and responses to the growth and survival cytokine IL-7. Expression of a critical component of the pre-B cell receptor, the surrogate light chain, is reduced in aged mice and IL-7 responsiveness is diminished. This predisposes the B cell precursors in aged mice to apoptotic cell death. These functions, and others important to B cell development, are governed, in part, via the transcriptional regulator E2A. E2A expression is also compromised in old age; this appears to involve enhanced degradation of E2A proteins. As a consequence of the B cell developmental deficits in old age, the repertoire of antibody specificities is skewed and capacity to develop effective immune responses is hindered.
- The molecular deficits which underlie dysfunctions in lymphocyte activity during old age have yet to be well characterized. These findings that expression of a transcription factor (E47) and surrogate light chains, both of which are critical to B lineage cell development, are decreased in aged B cell precursors provides a molecular basis for understanding deficient lymphopoiesis in senescence.
Selected Cancer-Related Publications
- Alter-Wolf S, Blomberg BB, Riley RL. Deviation of the B cell pathway in senescent mice is associated with reduced surrogate light chain expression and altered immature B cell generation,phenotype,and light chain expression. J Immunol 182:138-47, 2009. Read more »
- Landin AM, Frasca D, Zaias J, Van der Put E, Riley RL, Altman NH, Blomberg BB. Effects of fenbendazole on the murine humoral immune system. J Am Assoc Lab Anim Sci 48:251-7, 2009. Read more »
- Alter-Wolf S, Blomberg BB, Riley RL. Old mice retain bone marrow B1 progenitors,but lose B2 precursors, and exhibit altered immature B cell phenotype and light chain usage. Mech Ageing Dev 130:401-8, 2009. Read more »
- King AM, Keating P, Prabhu A, Blomberg BB, Riley RL. NK cells in the CD19(-) B220(+) bone marrow fraction are increased in senescence and reduce E2A and surrogate light chain proteins in B cell precursors. Mech Ageing Dev 130:384-92, 2009. Read more »
- Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, Blomberg BB. B cells and aging: molecules and mechanisms. Trends Immunol 30:313-8, 2009. Read more »
Collaborating in the Multidisciplinary Research Program(s):