GSBS Dissertations and Theses

Approval Date

March 1988

Document Type

Doctoral Dissertation

Department

Graduate School of Biomedical Sciences, Immunology

Subjects

Receptors, Antigen, B-Cell; Major Histocompatibility Complex; Academic Dissertations

Abstract

An optimal antibody response to a thymus-dependent antigen requires cooperation between the B cell and an antigen-specific helper T cell. Major histocompatibility complex restriction of this interaction implies that the helper T cell recognizes antigen on the B cell surface in the context of MHC molecules, and that the antigen-specific B cell gets help by acting as an antigen presenting cell for the helper T cell. However, a number of studies have shown that normal resting B cells are ineffective as antigen presenting cells, implying that the B cell must leave the resting state before it can interact specifically with a helper T cell. On the contrary, other studies, including those using rabbit Ig as antigen, and rabbit globulin-specific mouse T cell lines and hybridomas, show that certain T cell lines can be efficiently stimulated by normal resting B cells.

One possibility I considered was that small B cells are unable to process antigens, and that the rabbit Ig-specific T cell lines used above recognize native antigen on the B cell surface. In the majority of cases, experiments with B cell lines and macrophages have shown that antigen presentation requires antigen processing, a sequence of events which includes: internalization of antigen into an acid compartment, denaturation or digestion of antigen into fragments, and the return of processed antigen to the cell surface where it can then be recognized by the T cell in the context of class II molecules of the MHC.

The experiments reported here show that the rabbit Ig-specific T cell lines do require an antigen processing step, and that small resting B cells, like other antigen presenting cells, process antigen before presenting it to T cells. Specifically, I show that an incubation of 2-8 hours is required after the antigen pulse before antigen presentation becomes resistant to fixation or irradiation. Shortly after the pulse, the antigen enters a pronase resistant compartment. Chloroquine, which raises the pH of endocytic vesicles, inhibits presentation. In addition, a large excess of antibody to native antigen fails to block presentation of antigen after a 2-8 hour incubation. Also, although membrane Ig, the antigen receptor on the B cell, is required for efficient presentation of antigen at low concentrations, antigen is no longer associated with the B cell receptor at the time of presentation to the T cell. Modulation of membrane Ig by anti-Ig blocks presentation before but not after the antigen pulse.

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Copyright is held by the author, with all rights reserved.

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