Considerable effort has been directed toward the identification and understanding of lymphocyte populations capable of regulating antibody secreting B cell responses. In most cases the cells which augment or suppress B cell responses are of the T cell lineage. Nevertheless, recent work has indicated that another type of lymphocyte population, herein referred to as BH, is apparently capable of helping the response of some antibody secreting B cell populations. This unique cell population is obtained from spleens of normal mice and expresses determinants characteristics of both B (immunoglobulin, Ia, Lyb-3) and T (Lyt-1) lymphocytes. Its function is to specifically help the response of a subset of antibody secreting B cells which express complementary idiotypic determinants. The specificity of this helper activity is apparently a consequence of the ability of the BH population to bind idiotypic determinants. Recently, work from our laboratory as well as others has suggested that cells which phenotypically and functionally resemble BH cells play an important role in autoimmunity and neoplasia. This proposal extends the previous descriptive work on Lyt-1+ Ig+ cells to evaluate the role of these unique cells in the immune response and the mechanisms by which they interact with other cell populations in fulfilling their apparent regulatory function. Specifically, the questions to be addressed include: 1) What are the genetic requirements for BH cell dependent helper activity? 2) Does the T cell function associated L3T4 antigen play a role in BH cell dependent helper activity? 3) Are immunoglobulin bearing hybridomas which produce BH cell replacing factors representative of BH cells? 4) What is the nature of factors produced by BH hybridomas? 5) How do these factors relate to lymphokines described in other systems? 6) Can inducible BH clones be produced? 7) What is the role of BH cells in autoimmunity? The successful completion of these studies will result in an evaluation of how Lyt-1+, Ig+BH cells fit into the scheme of immune regulation in general and the idiotype network hypothesis in particular.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023978-02
Application #
3136616
Study Section
Immunobiology Study Section (IMB)
Project Start
1987-04-01
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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Peng, B; Sherr, D H; Mahboudi, F et al. (1994) A cultured malignant B-1 line serves as a model for Richter's syndrome. J Immunol 153:1869-80
Hardin, J A; Gibson, M; Grant, E et al. (1992) Interleukin 4 induces the maturation of idiotype-specific regulatory B cell populations. Proc Soc Exp Biol Med 200:383-93
Hardin, J A; Hinoshita, F; Sherr, D H (1992) Mechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis. Toxicol Appl Pharmacol 117:155-64
Hinoshita, F; Hardin, J A; Sherr, D H (1992) Fluoranthene induces programmed cell death and alters growth of immature B cell populations in bone marrow cultures. Toxicology 73:203-18
Hardin, J A; Sherr, D H; DeMaria, M et al. (1992) A simple fluorescence method for surface antigen phenotyping of lymphocytes undergoing DNA fragmentation. J Immunol Methods 154:99-107
Hardin, J A; Vos, K; Kawano, Y et al. (1990) A function for Ly-1+ B cells. Proc Soc Exp Biol Med 195:172-82
Hardin, J A; Gibson, M; Kawano, Y et al. (1990) Characterization of a B cell helper factor(s) derived from CD5+ B cell hybridomas. Cell Immunol 126:304-21
Gibson, M; Hardin, J A; Sherr, D H (1990) A CD5+ B cell hybridoma derived factor(s), which induces maturation of CD5+, idiotype-specific B-cell populations. J Mol Cell Immunol 4:241-51;discussion 251-3