title: Absence of memory B cells in patients with common variable immunodeficiency.
abstract: The molecular basis of common variable immunodeficiency (CVID) is unknown. To assess humoral immunity in CVID, we selected 24 patients with early or late onset of disease. X-linked agammaglobulinemia (XLA), X-linked hyper-IgM syndrome (XHIM), and non-XHIM were excluded based on clinical phenotype, assessment of the immune response, presence of Bruton's tyrosine kinase (Btk) in monocytes or platelets, and normal expression of CD40 ligand by activated T cells. The number of circulating B cells was within the normal range or reduced. IgD(-) CD27(+) memory B cells were markedly reduced or absent in all 24 patients and IgD(+) CD27(+) B cells were diminished in 8 patients. Circulating B cells from all 6 patients examined, including CVID patients with IgD(+) CD27(+) cells, failed to undergo somatic hypermutation in immunoglobulin-variable (V)-region genes, similar to cord blood B cells. B cells from CVID patients produced IgM and IgG, but not IgA upon the engagement of Ig receptor and CD40 in the presence of IL-2 and IL-10. B cells from all but 5 patients secreted IgE when stimulated by CD40 crosslinking in the presence of IL-4. The observation of defective memory B cells with abnormal cell marker expression and function demonstrates that naive CVID B cells including those expressing IgD(+) CD27(+), in analogy to cord blood and hyper-IgM syndrome B cells, may be responsible for their failure to differentiate into plasma cells and to produce high-affinity antibodies of different isotypes.
authors: Department of Infectious Immunology, Graduate School of Medicine, Matsumoto, Shinshu University, Japan. agemats@gipac.shinshu-u.ac.jp
authors: Kazunaga
authors: K
authors: Agematsu
authors: Takeshi
authors: T
authors: Futatani
authors: Sho
authors: S
authors: Hokibara
authors: Norimoto
authors: N
authors: Kobayashi
authors: Masaya
authors: M
authors: Takamoto
authors: Satoshi
authors: S
authors: Tsukada
authors: Harumi
authors: H
authors: Suzuki
authors: Shigeo
authors: S
authors: Koyasu
authors: Toshio
authors: T
authors: Miyawaki
authors: Kazuo
authors: K
authors: Sugane
authors: Atsushi
authors: A
authors: Komiyama
authors: Hans D
authors: HD
authors: Ochs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000502:physiology*; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D003564:Cytidine Deaminase / Q000235:genetics; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D007072:Immunoglobulin D; D007136:Immunoglobulins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D003564:Cytidine Deaminase