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B cell-dependent TCR diversification.

Cristina João1, Brenda M Ogle, Carlota Gay-Rabinstein

  • 1Transplantation Biology Program, Mayo Clinic, Rochester, MN 55905, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|April 7, 2004
PubMed
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B cells and their antibodies (Ig) are crucial for generating T cell diversity. Mice lacking B cells show drastically reduced T cell receptor diversity, which can be restored by adding diverse B cells or polyclonal Ig.

Area of Science:

  • Immunology
  • T cell biology
  • B cell function

Background:

  • T cell diversity was traditionally attributed to T cell interactions with thymic epithelial cells.
  • Emerging evidence suggests other cell types influence T cell diversity during development.
  • The identity of these influencing cells remained unknown prior to this study.

Purpose of the Study:

  • To investigate the role of B cells and immunoglobulin (Ig) in the generation of T cell diversity.
  • To determine if B cells and Ig are essential drivers of T cell receptor (TCR) repertoire diversity.

Main Methods:

  • Analysis of TCR V beta diversity in thymocytes of mice genetically deficient in B cells and Ig.
  • Comparison with wild-type mice and mice with oligoclonal B cell populations.

Related Experiment Videos

  • Assessment of thymocyte diversity following adoptive transfer of B cells or administration of Ig.

    • Main Results:

    • TCR V beta diversity in thymocytes was severely reduced (to 6 x 10^2) in mice lacking B cells and Ig, compared to wild-type (1.1 x 10^8).
    • Mice with oligoclonal B cells exhibited only 0.01% of wild-type thymocyte TCR V beta diversity.
    • Adoptive transfer of diverse B cells or polyclonal Ig increased thymocyte diversity 8- and 7-fold, respectively, in B cell-deficient mice.
    • Monoclonal B cells or monoclonal Ig did not significantly restore diversity.

    Conclusions:

    • B cells and Ig play a vital, previously unrecognized role in generating T cell diversity.
    • This interaction is essential for a broad T cell receptor repertoire.
    • Findings suggest a novel strategy for immune reconstitution by leveraging B cell and Ig functions.