Publication Date

Spring 2012

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Advisor

Tzvia Abramson

Keywords

flow cytometry, Inflammatory Bowel Disease, memory B cell, plasmablast, trafficking receptor, ulcerative colitis

Subject Areas

Immunology; Microbiology; Biology

Abstract

Background: The incidence of pediatric ulcerative colitis (UC), a chronic autoinflammatory disease of the colon, is on the rise. Although an increased infiltration of B cells from the peripheral blood into the colon occurs in UC, B cell trafficking is understudied. We hypothesized that the frequency of circulating plasmablasts (PBs) and their trafficking receptor (TR) expression may be indicative of the location and degree of pathology in pediatric UC. Methods: We conducted multicolor flow cytometry analyses of circulating IgA+/- PBs and IgA+ memory B cells (MBCs) in pediatric UC patients with remission, mild, moderate, and severe disease (n=12) and healthy pediatric (n=2) and adult donors (n=11). Results: Compared to healthy donors the average frequency of PBs among total peripheral blood lymphocytes increased 30-fold during severe UC activity and positively correlated with Pediatric Ulcerative Colitis Activity Index score, C-reactive protein level, and erythrocyte sedimentation rate. A greater percent of PBs in severe patients expressed the gut-homing receptors α4β7 and CCR10, and the inflammatory homing molecule P-selectin ligand (P-sel lig). The percent of IgA+ MBCs expressing α4β7, however, was reduced. Furthermore, expression of the small intestine TR CCR9 decreased on α4β7high PBs and on α4β7high/CCR10high PBs and MBCs in these patients, consistent with preferential cell targeting to the colon. Conclusions: Peripheral blood PBs with a colon-homing phenotype (α4β7/CCR10/P-sel lig) were elevated in children with severe UC. Screening this B cell subset may provide a complementary approach in monitoring disease activity or therapeutic efficacy in pediatric UC.

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