SOLUBLE-ANTIGEN PROFOUNDLY REDUCES MEMORY B-CELL NUMBERS EVEN WHEN GIVEN AFTER CHALLENGE IMMUNIZATION
- Author(s)
- Nossal, GJV; KARVELAS, M; Pulendran, B;
- Details
- Publication Year 1993-04-01,Volume 90,Issue #7,Page 3088-3092
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- The splenic B-cell repertoire of unimmunized C57BL/6 mice can be examined for anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) B cells of relatively high affinity by using a dual strategy. First, limiting numbers of splenocytes are polyclonally activated by Eschericia coli lipopolysaccharide and a mixture of interleukins 2, 4, and 5 in the presence of 3T3 filler cells, thus ensuring that many B-cell clones switch to IgG1 antibody production. Second, an enzyme-linked immunosorbent assay is geared to register only higher-affinity antibody by (i) detecting only bivalent IgG1 antibody and ignoring IgM and (ii) using a lowly substituted NP-conjugated protein as the capture layer. Naive spleens contain very few higher-affinity anti-NP B cells thus defined, but thymus (T)-dependent immunization causes the appearance of almost-equal-to 10(5) per spleen within 2 weeks. The development of these clonable anti-NP antibody-forming cell precursors can be virtually eliminated by a single injection of 1 mg of soluble, freshly deaggregated NP2-human serum albumin (HSA). This toleragen works not only if injected prior to challenge immunization, but even if given up to 6 days later. Soluble HSA works partially but not nearly as well as NP2-HSA, suggesting the possibility that the toleragen must act on T and B cells. NP conjugated to irrelevant carriers achieved partial tolerance in only one of four experiments. The studies demonstrate the need for continuing T-cell help throughout the process of memory B-cell generation. They also show that those recently activated T cells involved in this process can be silenced in vivo by soluble toleragen.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- IMMUNE-RESPONSE; LYMPHOCYTES-B; SOMATIC MUTATION; MICE; ANTIBODY; GENERATION; EXPRESSION; MOUSE; MATURATION; APPEARANCE
- Publisher's Version
- https://doi.org/10.1073/pnas.90.7.3088
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1993-04-01 12:00:00