We are studying the normal differentiation and regulatory interactions of B, T, and NK cells to gain information for analyzing lymphoid malignancies, immunodeficiency diseases, and other immunoregulation disorders. A large panel of monoclonal antibodies has been prepared against B-cell determinants, including antibodies to Ig isotypes, allotypes, and idiotypes and V?H? subgroups, as well as non-Ig determinants. These are used to define the genesis of pre-B and B cells in fetal liver and bone marrow and their subsequent migration and differentiation in peripheral lymphoid tissues. The therapeutic potential of anti-Ig antibodies is being explored in selected patients with B-cell malignancies. B-cell activation by anti-Ig antibodies in combination with various monokines and lymphokines is being explored. Ig isotype switching will be studied at both cellular and molecular levels in leukemic pre-B cell clones, cultures of mouse pre-B cells, and normal B cells. Our studies so far suggest that isotype switching is nonrandom and non-T cell dependent and usually involves direct switches from IgM to other isotypes; sequential isotype switching appears to be uncommon. Isotype-committed B cells were found to be selectively induced by helper T cells or soluble factors. Studies of human B cell and plasma cell malignancies suggest that these malignancies: (1) all have their origin in bone marrow; (2) involve a stepwise progression of transformation events; and (3) have clonal involvement prior to isotype switching. Children with pre-B leukemia were shown to have a significantly poorer prognosis than children with """"""""null"""""""" cell leukemia, and this may be associated with a chromosomal 1;19 translocation. A monoclonal antibody, HNK-1 or Leu 7, was prepared against a cell surface molecule of 110 kilodaltons, which is selectively expressed by human granular lymphocytes having NK cell activity. It has been used to examine the development, distribution, and function of NK cells and to define functionally deficient NK cells in patients with Chediak-Higashi syndrome and AIDS. Hemophilia patients treated with Factor VIII concentrates were found to have an isolated increase in circulating T suppressor cells, and in some cases this has preceded the development of AIDS. (LB)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA016673-12
Application #
3092723
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1975-05-01
Project End
1990-04-30
Budget Start
1986-05-01
Budget End
1987-04-30
Support Year
12
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Baskin, J G; Powell Jr, T J; Srinivas, R V et al. (1995) Moloney leukemia virus-induced cell surface antigen mimicry by monoclonal antibodies. Immunol Res 14:292-316
Kerr, W G; Burrows, P D (1991) Stage-specific transcription of germline IgH C gamma and C alpha regions during human B cell differentiation. Int Immunol 3:1059-65
Bucy, R P; Chen, C H; Cooper, M D (1991) Analysis of gamma delta T cells in the chicken. Semin Immunol 3:109-17
Tilden, A B; Kraft, A S (1991) The effect of bryostatin 1 on human lymphocyte-mediated cytotoxicity. J Immunother (1991) 10:96-104
Schat, K A; Chen, C L; Calnek, B W et al. (1991) Transformation of T-lymphocyte subsets by Marek's disease herpesvirus. J Virol 65:1408-13
Cooper, M D; Chen, C L; Bucy, R P et al. (1991) Avian T cell ontogeny. Adv Immunol 50:87-117
Wu, Q; Li, L; Cooper, M D et al. (1991) Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3. Proc Natl Acad Sci U S A 88:676-80
Burrows, P D; Kubagawa, H; Nishimoto, N et al. (1991) Differences in human B cell differentiation. Adv Exp Med Biol 292:215-26
Yamamoto, J K; Ackley, C D; Zochlinski, H et al. (1991) Development of IL-2-independent feline lymphoid cell lines chronically infected with feline immunodeficiency virus: importance for diagnostic reagents and vaccines. Intervirology 32:361-75
Miyawaki, T; Butler, J L; Radbruch, A et al. (1991) Isotype commitment of human B cells that are transformed by Epstein-Barr virus. Eur J Immunol 21:215-20

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