Date of Award

4-2020

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. John Spitsbergen

Second Advisor

Dr. Thomas Rothstein

Third Advisor

Dr. Robert Eversole

Keywords

B-1 cells, autoreactivity, antibodies, immunology, VH4-34

Access Setting

Masters Thesis-Open Access

Abstract

B-1 cells are a unique population of lymphocytes, with distinct phenotypic and functional characteristics in comparison to conventional B-2 cells. B-1 cells are thought to be more closely related to the innate immune system than the adaptive, and B-1 cells constitutively secrete antibody that is recognized as broadly reactive with low levels of autoreactivity. The antibody heavy chain segment, VH4-34, is overutilized by the human B-1 cell population. VH4-34 antibodies are associated with autoreactivity, although not all VH4-34 antibodies are autoreactive. The primary objective of this study was to determine whether autoreactive forms of VH4-34 antibodies are localized only to the B-1 cell population, or whether VH4-34 antibodies are autoreactive wherever they are found. We obtained cells from healthy human donors, sorted cells individually, PCR amplified antibodies, and then cloned and expressed the antibodies. The monoclonal antibodies were then tested against a series of autoantigens to determine if B-1 or B-2 cells produced more autoreactive VH4-34-containing antibodies. Results suggested that B-1 cells did produce more autoreactive/polyreactive VH4-34-containing antibodies than memory B- 2 cells, though the population observed was small and more samples are required in order to provide statistical significance.

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