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Characteristics of human antibody repertoires following active immune responses in vivo

Author:
  • Mats Ohlin
  • C. A K Borrebaeck
Publishing year: 1996-05
Language: English
Pages: 583-592
Publication/Series: Molecular Immunology
Volume: 33
Issue: 7-8
Document type: Journal article
Publisher: Pergamon

Abstract english

Possibilities to develop human monoclonal antibody specificities have recently been much facilitated by improvements of human hybridoma technology but even more so by the emerging phage-display technique. However, until recently very little has been known about the characteristics at the molecular level of the induced, T cell-dependent human antibody response, frequently targeted by these techniques. Rather, the major part of available sequence information has been related to tumor-derived or autoreactive antibodies. We have now investigated high affinity, monospecific, human antibody repertoires as developed by hybridoma technology. The VH region gene usage among such in vivo-induced repertoires is in only some respects similar to that found in the total B cell population. A limited number of heavy-chain variable segment loci account for the majority of all induced antibodies. A particular VH gene locus (4-34) frequently employed by peripheral B cells and associated with autoreactive antibodies was rarely used by the induced repertoire. Furthermore, in particular antigen systems, V region usage differs from the total available repertoire, and heavy-chain CDR3 is generally longer among antibodies induced against foreign protein antigens than in the average B cell population. Light-chain gene usage is often restricted to just a few dominant genes frequently found among B cells in general. In comparison, variable regions derived by phage-display technology in some antigen systems display even longer heavy-chain CDR3 than hybridoma-derived antibodies. This technique also appears to select a different set of germline genes preferentially (both with respect to VH and JH) as compared to hybridoma technology. In summary, the T cell-dependent antibody response against foreign antigens appears to differ from the average circulating B cell in several ways, and thus does not seem to represent a random selection of the available repertoire.

Keywords

  • antibody variable domain
  • germline gene usage
  • human monoclonal antibodies
  • J segment
  • phage display
  • somatic mutation
  • T cell-dependent antibody response
  • V segment

Other

Published
  • ISSN: 0161-5890
Carl B
Carl Borrebaeck
E-mail: carl [dot] borrebaeck [at] immun [dot] lth [dot] se

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Department of Immunotechnology

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