An Antibody-Deficiency Syndrome Due to Mutations in the CD19 Gene

Four patients from two unrelated families with increased susceptibility to infection, hypogammaglobulinemia, and normal numbers of B cells in the blood were found to have mutations in the CD19 gene. CD19, a protein on the B-cell surface, forms a complex with other proteins that participates in the activation of B cells by antigens. Four patients from two unrelated families with increased susceptibility to infection, hypogammaglobulinemia, and normal numbers of B cells in the blood were found to have mutations in the CD19 gene. Primary antibody deficiencies, which are associated mainly with susceptibility to bacterial infections, can be caused by mutations in genes involved in B-cell differentiation. 1 Such genetic defects block the differentiation of immature B cells in bone marrow, thereby causing both a deficiency of mature B cells in the peripheral circulation and agammaglobulinemia. 2 – 8 In disorders involving defects in the maturation process of antigen-responsive B cells, by contrast, there are mature B cells in blood and a deficiency of some, but not all, immunoglobulin classes (dysgammaglobulinemia) or hypogammaglobulinemia. These disorders fall into two categories. The hyper-IgM syndromes are those in which a . . .