Patients with chronic granulomatous disease have a reduced peripheral blood memory B cell compartment.

Published

Journal Article

In this study, we have identified an altered B cell compartment in patients with chronic granulomatous disease (CGD), a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH activity. This is characterized by an expansion of CD5-expressing B cells, and profound reduction in B cells expressing the memory B cell marker, CD27. Both findings were independent of the age, genotype, and clinical status of the patients, and were not accompanied by altered CD5 and CD27 expression on T cells. Focusing on CD27-positive B cells, considered to be memory cells based on somatically mutated Ig genes, we found that the reduction was not caused by CD27 shedding or abnormal retention of CD27 protein inside the cell. Rather, it was determined that CD27-negative B cells were, appropriately, CD27 mRNA negative, consistent with a naive phenotype, whereas CD27-positive B cells contained abundant CD27 mRNA and displayed somatic mutations, consistent with a memory B cell phenotype. Thus, it appears that CGD is associated with a significant reduction in the peripheral blood memory B cell compartment, but that the basic processes of somatic mutation and expression of CD27 are intact. X-linked carriers of CGD revealed a significant correlation between the percentage of CD27-positive B cells and the percentage of neutrophils with normal NADPH activity, reflective of the degree of X chromosome lyonization. These results suggest a role for NADPH in the process of memory B cell formation, inviting further exploration of secondary Ab responses in CGD patients.

Full Text

Duke Authors

Cited Authors

  • Bleesing, JJ; Souto-Carneiro, MM; Savage, WJ; Brown, MR; Martinez, C; Yavuz, S; Brenner, S; Siegel, RM; Horwitz, ME; Lipsky, PE; Malech, HL; Fleisher, TA

Published Date

  • June 1, 2006

Published In

Volume / Issue

  • 176 / 11

Start / End Page

  • 7096 - 7103

PubMed ID

  • 16709872

Pubmed Central ID

  • 16709872

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.176.11.7096

Language

  • eng

Conference Location

  • United States