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Programmed DNA Rearrangements During Differentiation: Immunoglobulin Class Switching

Citation

Davis, Mark Morris (1981) Programmed DNA Rearrangements During Differentiation: Immunoglobulin Class Switching. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-04292005-082735

Abstract

The events of B-lymphocyte differentiation can be reconstructed in part through an analysis of the organization of heavy-chain genes isolated from B-cell tumors (myelomas). A mouse immunoglobulin alpha heavy-chain gene is shown to be composed of at least three non-contiguous segments of germline DNA -- a VH gene segment, a JH gene segment adjacent to the Cμ coding region, and a Cα gene segment. These gene segments are joined together by two distinct types of DNA rearrangements: variable region formation and immunoglobulin class switching. Three examples of IgM → IgA elass switching were examined and in each case a different site adjacent to Cμ and a different site adjacent to Cα were joined together in the process of switching. Two of the three Cμ sites shared significant homology to each other (15/25 nucleotides) and all three of Cα sites were highly homologous (22/30 nucleotides). We believe these sequences serve as recognition sites for class switching. Furthermore, the lack of homology between the Cα consensus sequence and sequences reported for Cγ1 and cγ2b recombination sites suggests that this process is mediated by class-specific recognition sequences and, presumably, class-specific regulatory mechanisms. A number of predictions and possible explanations of immune phenomena result from this observation. Apparently nonproductive DNA rearrangements, occurring in the same tumor lines, seem also to utilize some of the _same regulatory apparati. In addition, it appears that in one example, MClOl, class switching has progressed from Cμ → Cα → Cγ1. This switching pathway presents difficulties for the simple deletional model of CH switching.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:antibody gene rearrangement, heavy chain switching ; immunoglobin ; DNA rearrangements
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Molecular Biology
Awards:Milton and Francis Clauser Doctoral Prize, 1981
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Hood, Leroy E. (advisor)
  • Lewis, Edward B. (co-advisor)
Thesis Committee:
  • Lewis, Edward B.
  • Davidson, Eric H.
  • Delbruck, Max
  • Davidson, Norman R.
  • Maniatis, Thomas P.
Defense Date:28 August 1980
Non-Caltech Author Email:mmdavis (AT) stanford.edu
Record Number:CaltechETD:etd-04292005-082735
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-04292005-082735
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1544
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:29 Apr 2005
Last Modified:28 Apr 2017 20:31

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