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Characteristics of human antibody repertoires following active immune responses in vivo

Ohlin, Mats LU and Borrebaeck, C. A K LU (1996) In Molecular Immunology 33(7-8). p.583-592
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
keywords
antibody variable domain, germline gene usage, human monoclonal antibodies, J segment, phage display, somatic mutation, T cell-dependent antibody response, V segment
in
Molecular Immunology
volume
33
issue
7-8
pages
10 pages
publisher
Pergamon
external identifiers
  • Scopus:0030152049
ISSN
0161-5890
DOI
10.1016/0161-5890(96)00018-1
language
English
LU publication?
yes
id
e2cfc3ba-ac2d-466d-b0af-6937ef65246a
date added to LUP
2016-04-19 14:08:22
date last changed
2016-04-22 13:29:39
@misc{e2cfc3ba-ac2d-466d-b0af-6937ef65246a,
  abstract     = {<p>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.</p>},
  author       = {Ohlin, Mats and Borrebaeck, C. A K},
  issn         = {0161-5890},
  keyword      = {antibody variable domain,germline gene usage,human monoclonal antibodies,J segment,phage display,somatic mutation,T cell-dependent antibody response,V segment},
  language     = {eng},
  number       = {7-8},
  pages        = {583--592},
  publisher    = {ARRAY(0x8fa6288)},
  series       = {Molecular Immunology},
  title        = {Characteristics of human antibody repertoires following active immune responses in vivo},
  url          = {http://dx.doi.org/10.1016/0161-5890(96)00018-1},
  volume       = {33},
  year         = {1996},
}