Murine CR1/2 targeted antigenized single-chain antibody fragments induce transient low affinity antibodies and negatively influence an ongoing immune response

Adv Exp Med Biol. 2007:598:214-25. doi: 10.1007/978-0-387-71767-8_15.

Abstract

We have generated a single-chain antibody which recognizes murine CR1/2 and carries a genetically fused influenza hemagglutinin derived peptide. Theoretically such a construct is able to crosslink the B cell antigen receptor and CR1/2 on peptide specific B cells. The construct was able to reach its CR1/2 positive target cells, yet intraperitoneal delivery of the construct elicited an IgM response only slightly exceeding that induced by the free peptide. Providing T cell help by the injection of peptide specific lymphocytes did not alter the response in essence, that is anti-peptide IgG was not detectable even after booster immunizations. When used as a booster vaccine following injection of the peptide in adjuvant, the construct even inhibited the development of IgG1 and IgG3 anti-peptide antibodies. These data indicate that although targeting of antigen to CR1/2 on B cells can enhance transient proliferation or differentiation of antigen specific B cells it cannot induce strong, longlasting humoral immune responses. Furthermore, CR1/2 targeting constructs may negatively influence an ongoing immune reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • B-Lymphocytes / immunology
  • Hemagglutinins, Viral / genetics
  • Hemagglutinins, Viral / immunology
  • Immunoglobulin Fragments / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Peptides / genetics
  • Peptides / immunology
  • Receptors, Complement 3b / genetics
  • Receptors, Complement 3b / metabolism*
  • Receptors, Complement 3d / genetics
  • Receptors, Complement 3d / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Spleen / cytology
  • Spleen / metabolism
  • T-Lymphocytes / immunology

Substances

  • Antibodies
  • Hemagglutinins, Viral
  • Immunoglobulin Fragments
  • Peptides
  • Receptors, Complement 3b
  • Receptors, Complement 3d
  • Recombinant Fusion Proteins