Specific antibody production by V-H-gene replacement

Citation
Mk. Madan et al., Specific antibody production by V-H-gene replacement, EUR J IMMUN, 30(8), 2000, pp. 2404-2411
Citations number
36
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
00142980 → ACNP
Volume
30
Issue
8
Year of publication
2000
Pages
2404 - 2411
Database
ISI
SICI code
0014-2980(200008)30:8<2404:SAPBVR>2.0.ZU;2-W
Abstract
V-H-gene replacement is a recombination event in which a pre-existing immun oglobulin heavy chain gene can be altered by the replacement of the rearran ged V-H gene segment with another V-H gene segment. Although this event has been demonstrated in various model systems, its role in generating antibod y diversity is still unsettled. We have used a genetically modified mouse s train, QM, with a quasi monoclonal primary B cell repertoire specific for N P to determine whether V-H gene replacement can generate a new antigen spec ificity. Hybridomas generated from QM splenocytes alter immunization with d ifferent antigens, gave rise to antibodies with specificity to the immunizi ng antigen or with new specificities. We found V-H-gene replacement was use d to change the original heavy chain gene rearrangement specific for NP int o a heavy chain gene encoding the new antigen specificity. V-H-gene replace ment intermediates were detected both before and after the immunization, su ggesting that the event was selective rather than instructive. These result s demonstrate that V-H-gene replacement can generate a new antibody heavy c hain gene with a different functional and selectable antigen specificity.