Analysis of sera specific for human B cells.
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Biomedical subjects
Publications and source records attributed to F E Ward.
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An sRBC-hemolysin monolayer was employed for separating human lymphocytes into two sub-populations, adherent cells (predominantly B cells) and non-adherent cells (predominantly T cells). The separated cells were then tested simultaneously against predispensed sera by complement-mediated cytolysis for the presence of alloantibodies to either T or B cells. A total of 372 sera were screened. Antibodies specific for B cell antigens were found in 19 sera and 9 sera were found to contain antibodies to T-specific antigens.
The polymorphic HL-A histocompatibility system has been studied in North American black families. The family studies show that haplotype frequencies differ between black and white populations. Seven haplotypes (W28,W5; W28,W17; W28, undefined four; W23,W5; W19,W5; undefined LA,W5; and undefined LA, undefined four) were significantly more frequent in blacks than whites, while haplotypes 1,8 and 3,7 were significantly less frequent. Some of these differences may be accounted for by differences in gene frequencies between the two groups; other differences may be explained by linkage disequilibrium in the white population. No significant linkage disequilibrium between the LA and FOUR loci was found in the black population.
Fifty-nine recipients received renal allografts from an HL-A haploidentical family member. Immunogenicity of the incompatible haplotype was measured by skin grafts exchanged within each family when possible, and renal allograft recipients were assigned prospectively to two groups depending on the skin graft survival time (Group 2A greater than 15 days; Group 2B less than 15 days). If skin grafts could not be accomplished, the patients were place in an unclassified group, Group 2. Renal function at one and 2 years following engraftment did not differ between the two groups. Mixed lymphocyte stimulation of recipient lymphocytes by mitomycin-treated donor lymphocytes also was comparable in the groups. Histopathological evaluation by light, immunofluorescence, and electron microscopy at least 6 months following allografting did not distinguish between the groups. The only differentiating characteristic was that Group 2A patients did not experience their primary rejection episode until an average of 18 days following transplantation, whereas Groups 2B and unclassified 2 had their initial primary rejection episode at average days 9 and 5, respectively. In our clinical program, matching for HL-A halotypes continues to be the best predictor for long-term renal function in consanguineous renal transplantation.
The Southeastern Regional Organ Procurement Program has developed a computerized system for the selection of organ transplant recipients. This system has proven to be a useful method for the rapid selection of histocompatible recipients for organ transplants from a large pool of potential recipients in a wide geographical area. In addition, the system provides a readily accessible source of data that can be used to analyze the relationship between histocompatibility and transplant survival.
HL-A genotyping was accomplished in 30 families (8 black, 21 white, and 1 American Indian) based on serological results obtained by our ususal lymphocytotoxicity assays. Each family was further tested by an antiglobulin microcytotoxicity method. Segregation patterns obtained by the latter method, compared with those of the former, showed few discrepancies. HL-A-identical siblings were serologically similar by the antiglobulin assay with frequency of discordant reactions at the same level as that of our regular two-stage lymphocytotoxicity assay. The antiglobulin method was shown to be highly reproducible with 1.3% discordance between duplicate tests. Many sera employed in routine cytotoxicity testing gave positive reactions with all family members in the antiglobulin assay (39% all positive by antiglobulin versus 16% by the regular cytotoxicity test), so that this method has limited usefulness for routine HL-A typing. The antiglobulin assay may have particular value, however, for identifying HL-A haplotypes in families, especially non-Caucasian, which give infrequent positive reactions in the usual lymphocytotoxicity assays.
The HL-A antigens of a Chinese population now living on the island of Taiwan have been investigated with reagents obtained from and characterized in Caucasian populations and with antisera obtained from Chinese multiparous women. Both HL-A2, the most frequent specificity found, and HL-A9 appear highly heterogeneous in this Chinese population since groups of antisera used to define HL-A2 or 9 in Caucasians gave discordant reactions. Moreover, new associations were found using chi-square and cluster analyses, further demonstrating the complexity of HL-A in this Taiwanese population. Fourteen % of 1183 Chinese multipara sera and 237 sera from multiple tranfused individuals were lymphocytotoxic and could be placed by cluster analysis into three major groups.
The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developed in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.
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