ArticleThe Journal of experimental medicine1995
Random mutagenesis of two complementarity determining region amino acids yields an unexpectedly high frequency of antibodies with increased affinity for both cognate antigen and autoantigen.
Article in The Journal of experimental medicine, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- Testing the role of the FcγRIIB immunoreceptor tyrosine-based inhibitory motif in regulation of the B cell immune response.Immunity, inflammation and disease · 2015Article
- Construction of an artificially randomized IgNAR phage display library: screening of variable regions that bind to hen egg white lysozyme.Marine biotechnology (New York, N.Y.) · 2013Article
- Differential regulation of self-reactivity discriminates between IgG+ human circulating memory B cells and bone marrow plasma cells.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Self-tolerance checkpoints in CD4 T cells specific for a peptide derived from the B cell antigen receptor.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Initial clonal expansion of germinal center B cells takes place at the perimeter of follicles.Immunity · 2009Article
- Genetic correlates of autoreactivity and autoreactive potential in human Ig heavy chains.Immunome research · 2009Article
- Influence of Fas on the regulation of the response of an anti-nuclear antigen B cell clonotype to foreign antigen.International immunology · 2008Article
- Autoreactivity in human IgG+ memory B cells.Immunity · 2007Article
- The evolution of human anti-double-stranded DNA autoantibodies.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Lymph node germinal centers form in the absence of follicular dendritic cell networks.The Journal of experimental medicine · 1999Article
- Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase.Clinical and experimental immunology · 1998Article
- The transcriptional promoter regulates hypermutation of the antibody heavy chain locus.The Journal of experimental medicine · 1997Article
- The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody.The Journal of clinical investigation · 1996Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
To gain insight into the mechanism and limitations of antibody affinity maturation leading to memory B cell formation, we generated a phage display library of random mutants at heavy chain variable (V) complementarity determining region 2 positions 58 and 59 of an anti-p-azophenylarsonate (Ars) Fab. Single amino acid substitutions at these positions resulting from somatic hypermutation are recurrent products of affinity maturation in vivo. Most of the ex vivo mutants retained specificity for Ars. Among the many mutants displaying high Ars-binding activity, only one contained a position 58 and 59 amino acid combination that has been previously observed among the monoclonal antibodies (mAbs) derived from Ars-immunized mice. Affinity measurements on 14 of the ex vivo mutants with high Ars-binding activity showed that 11 had higher intrinsic affinities for Ars that the wild-type V region. However, nine of these Fabs also bound strongly to denatured DNA, a property neither displayed by the wild-type V region nor observed among the mutants characteristic of in vivo affinity maturation. These data suggest that ex vivo enhancement of mAb affinity via site-directed and random mutagenesis approaches may often lead to a reduction in antibody specificity that could complicate the use of the resulting mAbs for diagnostic and therapeutic applications. Moreover, the data are compatible with a hypothesis proposing that increased specificity for antigen, rather than affinity per se, is the driving force for formation of the memory B cell compartment.
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