B cell differentiation and lymphocyte surface phenotype in late onset hypogammaglobulinaemia.
Lymphocyte function and cell surface phenotype were examined in fifteen patients with late onset hypogammaglobulinaemia. The percentage of surface immunoglobulin-positive B cells in fourteen of the fifteen patients was in the normal range. Patients' B cells expressed MHC class II antigens at normal levels. For one patient, there was relatively high sIgD and low sIgM expression on B cells; the rest of the patients did not differ from controls in surface immunoglobulin density. The proportion of B cells positive for CD5 in patients was comparable to normal controls, and considerably less than in cord blood. However, the pattern of immunoglobulin isotype secretion in vitro by patients' B cells closely paralleled responses of cord blood B cells. Spontaneous secretion of IgM and IgG by patients' B cells was very low. Following polyclonal activation in the presence of autologous T cells, cells from thirteen patients secreted IgM within the normal range in response to at least one activator. The response of patients' purified B cells to IL-2 and gamma-IFN was variable. For four of six tested, B cells cultured with IL-2 and gamma-IFN together with polyclonal activators secreted normal levels of IgM. B cells from the other two patients secreted little or no IgM in response to these cytokines. For fourteen patients, IgG secretion following polyclonal activation remained low both when B cells were cultured with T cells or with a combination of IL-2 and gamma-IFN. IgG subclass imbalance was seen in one patient, whose cells secreted an unusually high proportion of IgG3, and undetectable IgG2 and IgG4; this pattern was consistent whether T cell help was provided by autologous or allogeneic T cells. Similarly purified B cells from this patient showed deficient IgG2 and IgG4 production in response to IL-2 and gamma-IFN.
Duggan-Keen
M F
MF
Division of Immunology, School of Pathological Sciences, University of Newcastle upon Tyne.
Bird
A G
AG
Bird
P
P
Smith
S W
SW
Givan
A L
AL
Calvert
J E
JE
D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology*; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018956:CD5 Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma