Bonnie Blomberg, Ph.D.
Associate Professor of Microbiology & Immunology
Description of ResearchRegulation of B cell function in aged mice: Dr. Blomberg's laboratory, in collaboration with Dr. Richard Riley in the department of Microbiology & Immunology, has shown decreased pre-B cell numbers and pre-B receptors in aged mice when compared with young mice (2-4 months of age). Aged mice, those greater or equal to about 80% of their full life span (22-24 months of age), have a poor immune response- one aspect of which is qualitatively poorer antibodies. They have found that the transcription factor, E47, a key regulator of B cells, is decreased in both aged bone marrow precursor B cells and splenic activated B cells. E47, also necessary for Ig class switch, is reduced in aged mice. The lab investigators, including Dr. Daniela Frasca, have begun to determine the molecular regulation of E47 in aged splenic B cells. This includes decreased mRNA stability of E47 via increased TTP (tristetraprolin) in aged stimulated mouse B cells. Their current studies will reveal the molecular and cellular causes of these defects in the aged humoral immune response and we, including a graduate student, Ana Marie Landin, are attempting to reverse these defects in genetically altered cells and mice.
Regulation of B cell function in elderly humans: the last few years we have expanded the work we have done in mice to humans, where we have shown that the same “biomarkers” we have discovered for a challenged B cell response in aged mice, lower IgM to IgG class switch recombination (CSR), lower AID (activation induced cytidine deaminase), the enzyme necessary for CSR, and lower E47, the transcription factor we have shown is most relevant for decreased AID and CSR in aging, are also lower in aged (65 or over) humans. We (Dr. Daniela Frasca and Maria Romero) have recently begun to correlate these with a poorer antibody and B cell response to the influenza vaccine, and test for other contributors to this (e.g. inflammation or hormonal stress).
Quality of the Immune System in Breast Cancer Patients in Response to Psychosocial Intervention (Cognitive Behavioral Stress Management, CBSM): Another project in Dr. Blomberg's laboratory is clinical research with breast cancer patients. In collaboration with Drs. Michael Antoni, Suzanne Lechner and Charles Carver in the Department of Psychology, Dr. Blomberg and her lab colleagues, especially Alain Diaz, are measuring the status of various immune parameters in the patients in response to psychosocial intervention (e.g., group therapy, stress reduction). We have shown that intervention patients have an improved immune response as seen by the ability of their T cells to proliferate in response to an antigen-specific receptor stimulus (anti-CD3), as well as increase TH1 cytokine production resulting from T cell stimulation. Currently we are also measuring serum inflammatory cytokines (e.g. TNFa, IL-6, IL-1b) in response to CBSM. Inflammatory cytokines have been shown to have a negative prognosis for many cancers. Current/future studies will be directed toward determining cell types, e.g. B cells, macrophages involved in generating the inflammatory cytokines as well as possibly measuring the tumor-specific immune response of these patients. These studies are important to allow optimal immune response in cancer patients which will better detect/destroy residual cancer, and allow better patient survival.
- Biomarkers for poor B cell responses in aged (and younger) mice and humans have been identified: CSR, AID, E47
- Poor AID also correlates/predicts a poor response to the influenza vaccine
- Breast cancer patients show improved immune response after psychosocial intervention
Selected Cancer-Related Publications
- Swain SL, Blomberg BB. Immune senescence: new insights into defects but continued mystery of root causes. Curr Opin Immunol :,2013 Read more »
- Ratliff M, Alter S, Frasca D, Blomberg BB, Riley RL. In senescence,age-associated B cells secrete TNF? and inhibit survival of B-cell precursors*. Aging Cell 12:303-11,2013 Read more »
- Frasca D, Romero M, Diaz A, Alter-Wolf S, Ratliff M, Landin AM, Riley RL, Blomberg BB. A Molecular Mechanism for TNF-?-Mediated Downregulation of B Cell Responses. J Immunol 188:279-86,2012 Read more »
- Landin AM, Frasca D, Harrison P, Scallan M, Riley RL, Blomberg BB. E47 retroviral rescue of intrinsic B-cell defects in senescent mice. Aging Cell 10:327-37,2011 [JIF 7.148] Read more »
Collaborating in the Multidisciplinary Research Program(s):