Affinity dependence of the B cell response to antigen: a threshold, a ceiling, and the importance of off-rate

Immunity. 1998 Jun;8(6):751-9. doi: 10.1016/s1074-7613(00)80580-4.

Abstract

Initiation and affinity maturation of the humoral immune response is driven by antigen interaction with BCR. To study how signaling and antigen presentation through BCR depend on antigen/BCR affinity, lysozyme-specific B cell transfectants were challenged with mutated lysozymes differing in their binding kinetics. For detectable triggering, the antigen/BCR complex needed a Ka > 10(6) M(-1) (dissociation half-life > approximately 1 s). Mutated lysozymes whose binding was below this threshold could nevertheless be presented if complexed with soluble antibody. Above the threshold, the concentration of antigen required to trigger a response decreased as the affinity (particularly dissociation half-life) increased. However, a plateau was reached at Kas > approximately 10(10) M(-1) (dissociation half-life > 0.5 hr), supporting the idea of a ceiling to affinity maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens / immunology*
  • B-Lymphocytes / immunology*
  • Binding Sites / immunology
  • Cell Line
  • Liposomes / immunology
  • Mice
  • Receptors, Antigen, B-Cell / immunology*
  • Signal Transduction / immunology*

Substances

  • Antigens
  • Liposomes
  • Receptors, Antigen, B-Cell