title: Familial predisposition to monoclonal gammopathies: deviations in B-cell biology.
abstract: Monoclonal gammopathies are associated with advancing age but a familial predisposition has been recognized for several decades. A functional phenotype, characterized by increased immunoglobulin (Ig) production after mitogen stimulation has been identified in healthy members of 4 families showing a predisposition toward IgM and IgG/IgA disorders. B cells from these hyperresponders do not show increased rates of Ig gene translocations and no aberrations were detected in an in vitro model of the germinal center reaction. Array-based comparative genome hybridization revealed deletions of Ig genes in peripheral blood B cells, as expected. In addition, random changes were detected throughout the genome, presumably reflecting off-target activation-induced cytidine deaminase (AID) activity. These random changes were significantly less prevalent in B cells from hyperresponders, indicating less exposure to the germinal center environment during maturation.
authors.affiliation: Faculty of Medicine, University of Iceland, Reykjavík, Iceland. helgaogm@hi.is
authors.forename: Helga M
authors.initials: HM
authors.lastname: Ögmundsdóttir
authors.forename: Sóley
authors.initials: S
authors.lastname: Valgeirsdóttir
authors.forename: Heather R
authors.initials: HR
authors.lastname: Schiffhauer
authors.forename: Lóa Björk
authors.initials: LB
authors.lastname: Óskarsdóttir
authors.forename: Hlíf
authors.initials: H
authors.lastname: Steingrímsdóttir
authors.forename: Vilhelmína
authors.initials: V
authors.lastname: Haraldsdóttir
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D005190:Family; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D020022:Genetic Predisposition to Disease; D018858:Germinal Center; D006801:Humans; D010265:Paraproteinemias / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014178:Translocation, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051997:ADP-ribosyl Cyclase 1