ABSTRACT
Technical aspects of generation of antibody-secreting human-human hybridomas are evaluated as based on 100 human-human fusions with a human B-lymphoma cell line (RH-L4) or the SKO-007 myeloma cell line as malignant fusion partners, and compared with similar fusion conditions in the mouse hybridoma system. The yield of hybrids was significantly lower when normal peripheral blood lymphocytes were used as fusion partners as compared with spleen lymphocytes, but could be substantially improved by increasing the amount of mitotic active B-lymphocytes by mitogen stimulation of the lymphocytes, preferably in HAT medium, prior to fusion. Furthermore, human hybrids grew slower and had a higher degree of chromosomal instability than usually observed in the mouse hybridoma system. Thus, out of 72 fusions, only 3 stable hybrids with antibody production against a predefined antigen were established. The importance of improved sources of human B-lymphocytes for human-human hybridoma production is discussed and methods of obtaining such improvement suggested.
Subject(s)
Antibodies, Monoclonal/isolation & purification , Hybridomas/immunology , Animals , B-Lymphocytes/immunology , Cell Fusion , Cell Line , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunologic Techniques , Karyotyping , Lymphocyte Activation , Lymphoma/immunology , Mice , Mice, Inbred Strains , Plasmacytoma/immunologySubject(s)
Forced Expiratory Volume , Genetic Markers , Respiratory Tract Diseases/genetics , ABO Blood-Group System/genetics , Adult , Blood Group Antigens/genetics , Blood Proteins/analysis , Chronic Disease , Female , HLA Antigens/analysis , Humans , Male , Middle Aged , Polymorphism, Genetic , SmokingABSTRACT
We have studied HLA markers in family with 2 "Probable" and 2 "possible" cases of Alzheimer disease over 3 generations. Three of them (two brothers and the father) present A29 C-B12 DR2 haplotype. It seems that it exists an association between HLA system and Alzheimer disease but we cannot define the character of this genetic linkage; the study of many families and sporadic cases will allow to define it.
Subject(s)
Alzheimer Disease/genetics , HLA Antigens/genetics , Alzheimer Disease/immunology , Female , Genetic Markers , Humans , Male , PedigreeABSTRACT
The Basques were previously shown to present a high frequency of HLA-B18 and BfF1, which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA-A1, Bw57, BfS, C4 F1S, DR7 and HLA-Aw30, Cw5, B18, Bf F1, C4Fs degree, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA-DR3: a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1, P less than 10(-11)). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%), and HLA-DR2 was not found. The silent allele C4s degree was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P less than 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.
