[Membrane characteristics and functional analysis of human T and B lymphocytes].

Despite the presence of normal numbersand distribution ofT and 8 lymphocytes and normallevels of serum immunoglobulins, a five-month.ald In-fant failed to show any evidence ofT"C&U; or B-een im-munity. In trying to identify a specific membrane ab-normality as a potential cause of the immunologicdysfunction. we examined the lateral mobility ofthe cell-surface receptor for concanavalin A. In con-trast to normal cells. in which the receptor is dis-tributed uniformly over the cell surface. the pa-tient's lymphocytes showed an unusually high acS combined immune deficiency (SCID) isa heterogeneous and uniformly fatal disordercharacterizedby the failure of specific humoral andcellular immunity to develop. 1... With rare excep-tion,'·' it presents with a marked impairment in theexpansion of cells ofT lineage; normal numbers of pe-ripheral blood lymphocytes and, indeed, devated.numbers of B lymphocytes often prevail despite theuniform presence of profound hypogammaglobulin-emia. Thus, the combined deficiency often reflects thefailure of T-precursor cells to mature; they !!howacrots at various stages of development, includ·ing a primacy failure of function of thymic epithelialcells.J.•We report on an infant with an unusual, inheritedform of SCID in the presence of normal numbers ofTand B cells. These cells had surface receptors thatwere indistinguishable from normal; after interactionwith a number of ligands, however, there was noT -membrane abnormality that resulted in failure totransmit or translate triggering signals from the sur-face membrane to the nucleus, we examined the Frolll the! Oivilion of lmmWIOlOIY. RGeV<:.b. lmtitlltc:, H01p1tal for SickChildreD. Toronto. and tbc: l>eputmeat of Phyaiolo&Y;, Univftty ot Co-n-II«UQ..I Hc:aJ.\b Coruer, Farmm~toll. CT (addn:a ~'~~Print roqllf:IU to Dr.Gelfand at the Oivi.lion of llllm!IDOlol)', Re1t:an:b. llwiNie. The Hospitalfor Siclc: Cllildlcn. $$$ Univonlty Ave.. Toronto, Ontano M5G IX3).S11ppornod by lflllltl from tbc Mo1ial Raoan:b Fo1111dation ofCmada(MT 487$). from tbo National FOWidatioD-Matl::b of Dimes (6-109), fromthe Nationallnwtuta. of Hc:al.th (CA-185$4) and from the Amoriean Can-cer SocXty (BC-11')) (Dr. GdJand is • n:o:ipioqt of a Q11ocD Elizabeth 11 Sc:t-cntiltAward. and Or. Olivu ora FacWty RCiellf'Ch Awm1 !rom the Amen-c::a.a. Callc:er Socioty).cumulation of concanavalin A receptors in surfacecaps. This capping abnormalitY appeared in bothT and e lymphocytes and was exaggerated bycolchicine. an inhibitor of microtubule assembly.These findings support the theory that plasma-membrane-cytoskeleton interactions have a role inthe expression of specific immunity; the findingsalso identify new areas that should be consideredin trying to understand the primary Immunodefi-ciency diseases. (N Engl J Med 301:1245-1249,1979) lateral mobility o£ a surface ligand, concanavalin A(con A)/ in the membranes of the patient's lympho-cytes. Under normal conditions, con A binds to uni-formly distributed receptors and maintains a uniformsurface distribution during short-periods of incubationat 37°C. • The patient's lymphocytes showed an un-usually high accumulation of con A rtteptors in sur-face caps during brief incubation with fluorescein-A. This capping abnormality was exaggerated by ex-posure of the cells to colchicine, which inhibits micro-tubule assembly. Our findings support the theory thatthe lymphocyte cytoskeleton has a role in the expres-sion of nonnal immune ~pensiveness, and revealnew clues to the pathogenesis of primary, inheriteddisorders of the immune system. A live-month-old boy, the secondbom of a ~neows mar-riage, was rd'o:m:d to the Hospital for Sick Children with :JUSpeetedimmunodeficiency. beca.UJe a brother h.ad died at the age of threeyean from parainlluenza Type 3 pneumoniW aftef' a lifclo~history or infec:tions. L.aboratory evaluation of the brother bad~ed. an alnence of lympboc:ytc•proliferativc ~ponsc to lcetituand allogeneic cdb: be bad normal immunCIIJ!Obulin lcvcb butweak. if any, antibody ~nscs.On admi»ion the patient was wcll. developed. wcll. nourished,and at the 60th percentile for height and 75th percentile for w~ht.There were no abncmnal finding:~ otber than a. difTUJe, Kaiy,macular ruh and a generalized paucity oflymphoid IU&11es. Resultsof routine laboratory tesu were entirely normal. Leveb of adeno-sine dcaminase .1;nd nucleoside phosphoryla:se in the red celb (kind·ly auayed by Dr. E. Giblen. Seattle. WA) were normal.When the p.atient was seven monda old, after the ,tudiadc::!Ciibed here were eornplctecl and the ~i:l of combined im·munoddieiency wa:~ established, he received a b30hl245-1249 (Dc:cembc:r 6), 1979