The effects of NK cells on the proliferation of B cells in individuals with rheumatoid arthritis.
Author
Ward, Diane Marie.Issue Date
1990Keywords
ImmunologyAdvisor
Yocum, David E.
Metadata
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The University of Arizona.Rights
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.Abstract
Natural killer cells (NK) belong to a heterogenous group of cells primarily thought to function against tumors. However, additional studies have indicated a broader role for these cells in immune regulation, including the regulation of B cells. Peripherial blood lymphocytes from rheumatoid arthritis (RA) patients and normal individuals were purified into three groups: T, B, and NK cells. Purity of these populations was assessed by Facs analysis (94%, 90% and 86% respectively.) These cells were used in a proliferative assay to determine the affects of NK cells on polyclonal proliferation of B cells. The normal and rheumatoid arthritis patients were previously assessed in terms of a proliferative response to recall antigen and designated as either anergic (non-responsive) or non-anergic (responsive). Inhibition of B cell proliferative response was seen in the normal (-35% ± 4.5) and non-anergic subgroup (-25.6 ± 3.8), but not in the anergic subgroup (+11.2 ± 76.8). While removal of the CD57⁺ NK cells did not reverse the inhibition seen in the normal or non-anergic individuals, elimination of the CD16⁺ cells did (-1 ± 0.816 and 6.4 ± 6.5 respectively), with no significant effect on the anergic subpopulation. To investigate the dependence of this NK regulation on T cells, CD8⁺ T cells were removed. While there was no significant difference seen in the inhibition levels in the normal and non-anergic groups, inhibition in the anergic population significantly increased. This work suggests that NK cells are involved in limiting the proliferative response of activated B cells and this is dependent on the CD16⁺ subset of NK cells. While non-anergic rheumatoid arthritis individuals show no difference from the normal group in this function, anergic patients do, with the CD8⁺ T cells (suppressor/cytotoxic) subset apparently involved. Functional differences seen in the RA group were reflected by abnormal expression of cell surface antigens, as assessed in peripherial blood lymphocytes by Facs analysis. An increase in the expression of the CD8 marker in both the anergic and non-anergic individuals supports the hypothesis of an underlying T suppressor cell defect. Compensation by the two RA subgroups appears to be different. The anergic group had higher numbers of CD16⁺ cells, while the non-anergic group had NK cells that functioned at a higher level, as determined by the decrease expression of the CD56 marker in the surface of these cells. These data serve to reinforce the idea that individuals with RA belong to a heterogenous group.Type
textDissertation-Reproduction (electronic)
Degree Name
Ph.D.Degree Level
doctoralDegree Program
Microbiology and ImmunologyGraduate College