The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the “12/23” rule and the “beyond 12/23” rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with normal physiological and various pathological conditions by high-throughput sequencing. Our results showed that IGHJ gene frequency follows a similar pattern which is previously known, where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10∼20%), and IGH2/IGHJ1 is used at low frequency (<4%) under whether normal physiological or various pathological conditions. However, our analysis of the recombination signal sequences suggested that the conserved non-amer and heptamer and certain 23 bp spacer length may affect the initial IGHD-IGHJ recombination, which results in different frequencies of IGHJ genes among the initial BCR-H repertoire. Based on this “initial repertoire,” we recommend that re-evaluation and further investigation are needed when analyzing the significance and mechanism of IGHJ gene frequency in self-tolerance selection and the clonal proliferative response.
The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the "12/23" rule and the "beyond 12/23" rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with physiological and various pathological conditions by high-throughputsequencing. Our results showed that IGHJ gene frequency follows a similar pattern where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10%~20%), and IGH2/IGHJ1 is used at low frequency (<4%) under whether physiological or various pathological conditions. Furthermore, analysis of the recombination signal sequences suggested that the conserved nonamer and heptamer and certain 23 bp spacer length may affect the initial IGHD-IGHJ recombination, which results in different frequencies of IGHJ genes among the initial BCR-H repertoire. Based on this "background repertoire", we recommend that re-evaluation and further investigation are needed when analyzing the significance and mechanism of IGHJ gene frequency in self-tolerance selection and the clonal proliferative response.
Background: The screening efficiency of Erythrocyte indices varies in different regions. This study aimed to analyze the application efficiency of 11 Erythrocyte indices in Jiujiang prefecture. Methods: A total of 2379 patients with suspected thalassanemia were enrolled in Jiujiang Maternal and Child Health Hospital. Thalassanemia genes were detected by reverse dot blot hybridization. In addition, receiver operating characteristic curve (ROC) was used to analyze and calculate the sensitivity, specificity, Youden's Index(YI), positive likelihood ratio(+LR) , negative likelihood ratio(-LR) and area under curve (AUC) of the Erythrocyte indices. Results: 1)Thalassanemia carriers in Jiujiang prefecture mainly involved α- thalassanemia and β-thalassanemia, with the detection rate of 11.60%%. Thereinto, --SEA/αα(50.35%%) and -α3.7/αα(39.86%%) predominated in α-Thalassanemia, while the commonest gene mutation types of β-Thalassanemia were βIVS-II-654/βN, βCD41-42/βN, and βCD17/βN, accounting for 64.29%,15.87% and 9.542%, respectively. 2) Of 11 erythrocyte indices, Green and King (G&K) exhibited the highest diagnostic efficiency, with the AUC above 90%, a high sensitivity and a good specificity, which followed by England and Fraser (E&F), Sirdah(SI), Jayabose (RDW index) and Ricerca(RI). while Bessman), Ehsani(EI), Srivastava(Sriv), Shine and Lal (S&L), MentzIer(MI) and RBC count(in million) possessed a lower application value for thalassanemia screening. Conclusion: 1)Analysis of thalassanemia genotypes can provide a theoretical basis for thalassanemia screening, prenatal diagnosis and genetic counseling. 2)Compared with other erythrocyte indices, Green and King (G&K) showed higher application value for thalassanemia screening, with the largest AUC above 90%. which is considered feasible for thalassanemia screening in Jiujiang prefecture, Jiangxi province.
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