Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens

Elizabeth E. Eynon, David Parker

Research output: Contribution to journalArticle

391 Citations (Scopus)

Abstract

We have investigated the ability of resting B cells, acting as antigen-presenting cells, to induce tolerance to soluble protein antigens in mice, using an antigen targeted specifically to B cells. We inject mice intravenously with ultracentrifuged Fab fragments of rabbit anti-mouse immunoglobulin D (IgD) (Fab anti-δ). Treatment with Fab anti-δ results in profound tolerance to challenge with 100 μg Fab nonimmune rabbit Ig (Fab NRG), precipitated in alum, as measured by antibody production. Tolerance to rabbit Fab is antigen specific, since the treated mice make normal antibody responses to a control antigen, chicken Ig. Tolerance is dependent on antigen presentation by B cells, since intravenous injection of soluble Fab NRG, which is not targeted to B cells, results in a much lower frequency and degree of tolerance, especially at lower doses. T cell help in this system is affected, since T cells from Fab anti-δ-treated mice fail to provide help for an adoptive primary antibody response to Fab NRG when transferred together with normal B cells into severe combined immunodeficient (SCID) mice. The antigen-specific B cell compartment is also affected during tolerance induction, since B cells from treated animals make less antibody than normal B cells when transferred into SCID mice with normal T cells. Although the mechanism of nonresponsiveness in the helper T cell compartment remains to be determined, we think it is likely that the precursors of helper T cells are inactivated or deleted by encountering antigen presented by small, resting B cells, which lack accessory signals necessary to induce helper T cell proliferation and differentiation to effector function. Our experiments suggest a role for small B cells as antigen-specific, tolerizing antigen-presenting cells in acquired tolerance to foreign protein antigens and in self-tolerance to soluble self-proteins.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalJournal of Experimental Medicine
Volume175
Issue number1
StatePublished - 1992
Externally publishedYes

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Antigen-Presenting Cells
B-Lymphocytes
Antigens
Proteins
Rabbits
Helper-Inducer T-Lymphocytes
Antibody Formation
SCID Mice
T-Lymphocytes
Rho(D) Immune Globulin
Self Tolerance
Immunoglobulin Fab Fragments
Antigen Presentation
Intravenous Injections
Cell Differentiation
Chickens
Cell Proliferation
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. / Eynon, Elizabeth E.; Parker, David.

In: Journal of Experimental Medicine, Vol. 175, No. 1, 1992, p. 131-138.

Research output: Contribution to journalArticle

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