The effects of a model B cell superantigen on the immune response.

Format:

Book

Thesis/Dissertation

Author/Creator:

Kozlowski, Lisa Marie.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Immunology.

0982.

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Local Subjects:

Penn dissertations--Immunology.

Immunology--Penn dissertations.

0982.

Physical Description:

170 pages

Contained In:

Dissertation Abstracts International 58-07B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Over the past ten years, several antigens have been described that possess B cell superantigenic properties, including Staphylococcal protein A (SpA), HIV gp120, protein L, and protein Fv. Of these SAgs, SpA is the best characterized and has become the prototypic B cell SAg.

SpA binds not only to the Fc of IgG, but also to the Fab of Igs independent of heavy chain isotype. This binding, which occurs outside the conventional antigen binding groove, is restricted to human Igs using VH3 heavy chains and mouse Igs expressing S107 or J606 heavy chains.

In our studies, we used SpA or SpA hyperiodinated to abrogate its Fc binding ability (Mod SpA) as our model B cell SAg to examine the effect(s) of a B cell SAg on soluble and membrane-bound Igs in vitro and in vivo. We first investigated the ability of a B cell SAg, following an interaction with its reactive Igs, to activate the complement cascade. Our results provided the first direct evidence that an interaction of Mod SpA, as a B cell SAg, with its reactive (human VH3$\sp+)$ Igs leads to activation of the classical complement cascade. Next, we examined if the interaction of a B cell SAg with its reactive soluble Igs leads to tissue inflammation and damage in vivo. In a rabbit model of tissue inflammation, we provided evidence that SpA, as a B cell SAg, following an interaction with VH3$\sp+$ IgGs causes immune complex-mediated tissue inflammation.

Additionally, we wanted to explore the effect of a B cell SAg on the murine B cell repertoire following an interaction with membrane IgM. In vitro, we determined that Mod SpA on an insolubilized matrix causes activation of murine B cells when the cell population contains a high precursor frequency of Mod SpA-binding cells. A preliminary experiment in vivo indicated that neonatal administration of Mod SpA did not cause an increase in the number of Mod SpA-binding B cells. Further studies will be required to determine if these B cell superantigenic effects are relevant to the pathogenesis of clinical disease.

Notes:

Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 1997.

Source: Dissertation Abstracts International, Volume: 58-07, Section: B, page: 3545.

Local Notes:

School code: 0175.

ISBN:

9780591502046

Access Restriction:

Restricted for use by site license.