Hapten Binding by Lymphocyte Surface Immunoglobulin and the Subsequent Implications for Affinity Maturation
Jarvis, Michael Richard
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https://hdl.handle.net/2142/71154
Description
Title
Hapten Binding by Lymphocyte Surface Immunoglobulin and the Subsequent Implications for Affinity Maturation
Author(s)
Jarvis, Michael Richard
Issue Date
1982
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Microbiology
Abstract
Involvement of surface membrane immunoglobulin (smIg) in the elicitation of affinity maturation has been approached from a number of possible considerations. The salient features are summarized. First, retention time of antigen by membrane associated smIg involves assessment of geometric and probabilistic arguments, in addition to smIg affinity. The functional or observed association constant resulting from multi-determinant-smIg interaction (avidity) may provide a degree of enhancement in antigen binding as to obscure the selective advantage of intrinsic smIg affinity. Second, in the young New Zealand Black animal model, characterized by B lymphocyte hyperactivity (possibly due to T(,s) lymphocyte deficiency), the antibody affinity maturation process occurs at an accelerated rate when compared to another animal model (BALB/cV). Third, in a B cell plasmacytoma (MOPC-315) which had experienced isotype class switch to an (alpha) heavy chain, the immunoglobulin active site was identical between the cell's smIg and secreted immunoglobulin. Protein specificity and affinity for nitrophenyl compounds were determined by quantitative affinity chromatography. Therefore, smIg and secreted immunoglobulin active site identity appear to be a continuous and necessary feature of B cell selection and differentiation. Fourth, naive lymphocytes from BALB/cV mice, selected according to smIg avidity on fluorescein affinity plates failed to demonstrate on anti-fluorescyl response upon adoptive transfer into irradiated recipients. In contrast, selection of antigen-sensitized lymphocytes by affinity panning was effective in removal of certain cell populations. However, the resulting antibody produced from the reconstitution systems were similar in high affinity, regardless of the selected for smIg avidity. Fifth, hapten specific T lymphocytes appeared, within the constraints of the reconstitution system, not to influence antibody affinity maturation and therefore, probably did not influence B cell clonal selection and expansion. Carrier specific T lymphocytes were required for an anti-fluorescyl antibody response.
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