Immunological aspects of immunodeficiency diseases part 26

Mice deficient in BAFF or its receptor have  impaired B-cell development and antibody deficiency. TACI -/- mice have reduced serum IgA and IgM levels, reduced  antibody responses to T-cell-independent antigens, and tend to develop autoimmunity and B lymphoproliferation. Mutations in TACI have been found in CVID patients and their relatives, with selective IgA deficiency, indicating variable penetrance of this gene defect. In the majority of currently documented patients, TACI mutation affects only one allele, indicating a dominant negative effect of the mutation gene. A possible explanation is that TACI, like other members of the TNF-receptor family, undergoes ligand independent  preassociation and function as  multimeric units. Thus, incorporation of a mutated TACI chain in this multimeric complex may disrupt ligand binding or signal-transducing capacity. Recent studies have found that family members of CVID patients posessing heterozygous  TACI mutations may have completely normal serum immunoglobulin levels and "in vitro" B-cell function. This lead to the conclusion that the development of antibody deficiency in those carrying heterozygous TACI mutations may depend on modifier genes or environtmental factors.