Severe combined immunodeficiency in man with an absence of immunoglobulin gene rearrangements but normal T cell receptor assembly.
An autosomal recessive type of severe combined immunodeficiency disease (SCID) was characterized by an absence of immunoglobulins (Ig) in the serum and of Ig+ lymphocytes in bone barrow (BM) and peripheral blood. In the BM CD10+/terminal deoxynucleotidyl transferase-positive lymphocytes were identified. Epstein-Barr virus-transformed B lymphoblastoid cell lines (BLCL) obtained from BM and peripheral blood did not synthesize Ig. The Ig heavy and light chain gene complexes in the BLCL had retained the germ-line configuration. Mature T cells were present but their numbers in peripheral blood were decreased. T lymphoblastoid cells derived from peripheral blood expressed normal T cell receptor (TcR) CD3 complexes and manifested various genomic TcR rearrangements. It was concluded that this type of SCID entailed a complete arrest of B lymphocyte differentiation in an early stage prior to Ig rearrangements and a quantitative defect of T lymphocytes which nevertheless allowed development of mature T cells. Repeated failures of BM transplantation and the striking absence of Ig assembly suggested that this SCID defect resides in the BM microenvironment.
Thompson
A
A
Division of Immunobiology and Genetics, University Medical Center, Leiden, The Netherlands.
Hendriks
R W
RW
Kraakman
M E
ME
Koning
F
F
Langlois-van den Bergh
R
R
Vossen
J M
JM
Weemaes
C M
CM
Schuurman
R K
RK
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002472:Cell Transformation, Viral; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics
D015703:Antigens, CD; D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell