We have recently shown that low doses (200-300 rads) of ionizing irradiation selectively inhibit B cell responses to Class II thymus independent (TI) antigens without significantly affecting responses to Class I, TI antigens (3). We hypothesize this selective radiosensitivity is due to biochemical differences in B cell subpopulations, and may provide a new experimental approach to examine B cell development and heterogeneity in normal mice. We extended this functional analysis to mouse strains with genetic abnormalities known to affect B cell function to show genetic factors play a role in B cell resistance to ionizing irradiation. In mice which express the X-linked immunodeficiency trait xid, the entire response to TI antigens is highly radiosensitive; while in NZB mice both TI-1 and TI-2 responses are radioresistant. We propose three distinct types of experiments to determine the basis for these effects. Functional studies will: determine the kinetics of B cell recovery following irradiation; make a preliminary assessment of the genetic complexity of selective B cell radiosensitivity; and examine the contribution of microenvironment and ancillary cell types to B cell radiosensitivity. Secondly, we will define the B cell populations that are depleted by, or survive irradiation exposure, using a panel of carefully selected monoclonal antibodies to B cell surface antigens, to determine if functional changes in TI responses can be attributed to antigenically definable B cell subpopulations. Population changes will be monitored in spleen cell suspensions by flow cytometry, and in spleen microenvironments by immunohistochemistry. We will also use these techniques to monitor B cell regeneration following irradiation. Lastly, we propose to assess, preliminarily, the biochemical basis for selective B cell radiosensitivity by monitoring free radical induced plasma membrane damage, and the induction of endogenous endonuclease activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
9R01AI030890-07
Application #
3145876
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1990-08-01
Project End
1993-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655