Abstract

This is a request to continue studies that began over 26 years ago (the grant underwent a number change on my move to Dallas 21 years ago) on mechanisms of antibody diversity. Two new models allow us to challenge certain approaches to the developing repertoire: the minilocus transgenic mouse (developed under the auspices of this grant), and the human germinal center B cell (which we can now isolate from tonsils with ease). These two models provide us with the opportunity to challenge existing notions of diversity including insertion/deletion events and the utilization of the DIR gene segments. This is an amended application which attempts to deal with the major criticisms the study section found in the original: 1) the proposal is unfocused, 2) the issues being addressed are relatively uncommon, and 3) the approaches described are not likely to lead to an understanding of the underlying mechanisms. Hopefully the amended application will addresses each of these (and other issues) in a direct and satisfactory manner.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI012127-24A1
Application #
2657289
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1979-05-01
Project End
2002-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
24
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104

  Publications

Jackson, Stephen M; Harp, Natessa; Patel, Darshna et al. (2009) Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression. Blood 113:3999-4007
Jackson, Stephen M; Harp, Natessa; Patel, Darshna et al. (2007) CD45RO enriches for activated, highly mutated human germinal center B cells. Blood 110:3917-25
Jackson, S M; Harp, N; Patel, D et al. (2007) CD45RO: a marker for BCR-mediated selection. Scand J Immunol 66:249-60
Rahman, Negar S; Godderz, LeAnn J; Stray, Stephen J et al. (2006) DNA cleavage of a cryptic recombination signal sequence by RAG1 and RAG2. Implications for partial V(H) gene replacement. J Biol Chem 281:12370-80
Jackson, Stephen M; Capra, J Donald (2005) IgH V-region sequence does not predict the survival fate of human germinal center B cells. J Immunol 174:2805-13
Kolar, Grant R; Yokota, Takafumi; Rossi, Maria Isabel D et al. (2004) Human fetal, cord blood, and adult lymphocyte progenitors have similar potential for generating B cells with a diverse immunoglobulin repertoire. Blood 104:2981-7
Rodgers, William; Jordan, Stephen J; Capra, J Donald (2002) Transient association of Ku with nuclear substrates characterized using fluorescence photobleaching. J Immunol 168:2348-55
Carayannopoulos, M O; Potter, K N; Li, Y et al. (2000) Evidence that human immunoglobulin M rheumatoid factors can Be derived from the natural autoantibody pool and undergo an antigen driven immune response in which somatically mutated rheumatoid factors have lower affinities for immunoglobulin G Fc than thei Scand J Immunol 51:327-36
Frazer, J K; Jackson, D G; Gaillard, J P et al. (2000) Identification of centerin: a novel human germinal center B cell-restricted serpin. Eur J Immunol 30:3039-48
Tuaillon, N; Capra, J D (2000) Evidence that terminal deoxynucleotidyltransferase expression plays a role in Ig heavy chain gene segment utilization. J Immunol 164:6387-97

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