A single diversified VH gene family dominates the bovine immunoglobulin repertoire

1997 ◽  
Vol 25 (2) ◽  
pp. 326S-326S ◽  
Author(s):  
ROBERT AITKEN ◽  
JANICE GILCHRIST ◽  
M. CATHERINE SINCLAIR
Keyword(s):  
Gene Family ◽  
Vh Gene ◽  
Immunoglobulin Repertoire ◽  
Bovine Immunoglobulin

scholarly journals Diversity in the germline antibody repertoire. Molecular evolution of the T15 VN gene family.

1985 ◽  
Vol 162 (6) ◽  
pp. 1998-2016 ◽  
Author(s):  
R M Perlmutter ◽  
B Berson ◽  
J A Griffin ◽  
L Hood
Keyword(s):  
Gene Family ◽  
Gene Segment ◽  
Variable Region ◽  
Structural Features ◽  
Mouse Strains ◽  
Antibody Repertoire ◽  
Region Gene ◽  
Environmental Selection ◽  
P Gene ◽  
Vh Gene

The T15 heavy chain variable region (VH) gene family in BALB/c mice includes four elements each greater than 88% homologous with the other. One of these elements, V1, encodes virtually all of the VH regions in BALB/c antiphosphorylcholine antibodies, while another element, V3, is a pseudogene and cannot be transcribed or translated. We have examined the structural features of this VH gene family in other mouse strains and, in particular, have cloned and sequenced the alleles of these gene segments present in B10.P mice. Each of the four B10.P sequences can be matched with its allelic counterpart in BALB/c mice. This represents the first successful analysis of allelism in antibody variable region gene segments. The V1B10.P allele, like its BALB/c counterpart, encodes most of the known phosphorylcholine binding heavy chains from C37BL/6 mice. Similarly, the V3B10.P gene segment is a pseudogene like V3BALB, although only two of four abnormalities present in the BALB/c allele are also present in the B10.P allele. Careful analysis of the specific substitutions observed in the T15 VH gene family suggests that environmental selection for functional combining regions contributes significantly to the pattern of variation in the germline antibody repertoire. In addition, evidence is presented supporting frequent gene conversion events in the divergence of antibody genes.

Comparative study of VH gene family usage by newbornxid and non-xid mice, newborn NZB and adult NZB mice, and by splenic and peritoneal cavity B cell compartments

1988 ◽  
Vol 18 (12) ◽  
pp. 1979-1983 ◽  
Author(s):  
Guillaume Dighiero ◽  
Annick Lim ◽  
Marie-Pierre Lembezat ◽  
Azad Kaushik ◽  
Luis Andrade ◽  
...  
Keyword(s):  
Comparative Study ◽  
Gene Family ◽  
B Cell ◽  
Peritoneal Cavity ◽  
Cell Compartments ◽  
Vh Gene

Distinctive IgVH Gene Segments Usage and Mutation Status in Chinese Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4708-4708
Author(s):  
Lijuan Chen ◽  
Yaping Zhang ◽  
Wenjuuan Zheng ◽  
Jianyong Li ◽  
Changgeng Ruan
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Gene Family ◽  
Gene Families ◽  
Lymphocytic Leukemia ◽  
Chinese Patients ◽  
Chain Gene ◽  
Mutation Status ◽  
Significant Difference ◽  
Variable Heavy ◽  
Vh Gene

Abstract Chronic lymphocytic leukemia (CLL) is characterized by the relentless accumulation of monoclonal B cells with the appearance of small mature lymphocytes and a characteristic CD5 and CD19 co-expression immunophenotype. The incidence of CLL in Asian countries is lower than that in the Western ones, where CLL is the most common leukemia. To evaluate the frequency and mutation status of immunoglobulin (Ig) variable heavy chain gene (IgVH) expression in Chinese patients with CLL. We investigated IgVH gene segments usage and mutation status by multiplex RT-PCR in 52 CLL patients, and analyzed the relationship between IgVH somatic mutation status and the expression of CD38, ZAP-70 and CLLU1. 38 patients had mutated IgVH, and 14 had unmutated IgVH. The most frequently expressed VH gene family was found to be VH3 (46.2%) followed by VH4 (40.4%), VH1 (5.8%), VH2 (5.8%) and VH7 (1.9%), with no expression of VH5 and VH6 gene families. VH1-69 and VH3-21 which commonly overused in Western CLL weren’t detected in our cohort. The frequency of IgVH gene families indicates significant difference in Chinese CLL patients compared with Western patients, suggesting involvement of ethnic and/or environmental factors in CLL disease initiation. IgVH gene mutation status was significantly associated with the expression of CD38 and CLLU1. The expression of them may be simple and reliable surrogates for the identification of IgVH mutations. VH gene family usage and mutation status VH family n Mutated VH gene Unmutated VH gene VH1 3 3 0 VH2 3 2 1 VH3 24 19 5 VH4 21 16 5 VH5 0 0 0 VH6 0 0 0 VH7 1 0 1

Endogenous VH gene family expression in immunoglobulin-transgenic mice: evidence for selection of antibody repertoires

1991 ◽  
Vol 3 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Alf Grandien ◽  
Antonio Coutinho ◽  
Jan Andersson ◽  
Antonio A. Freitas
Keyword(s):  
Transgenic Mice ◽  
Gene Family ◽  
Vh Gene ◽  
Antibody Repertoires ◽  
Selection Of

scholarly journals Differential expression of VH gene families in peripheral B cell repertoires of newborn or adult immunoglobulin H chain congenic mice.

1992 ◽  
Vol 175 (6) ◽  
pp. 1449-1456 ◽  
Author(s):  
A C Viale ◽  
A Coutinho ◽  
A A Freitas
Keyword(s):  
Gene Family ◽  
B Cell ◽  
Expression Pattern ◽  
Gene Families ◽  
Cell Repertoire ◽  
Adult Mice ◽  
Igh Locus ◽  
B Cell Repertoire ◽  
Vh Gene ◽  
Old Mice

The pattern of VH gene family expression in the primary B cell repertoire of the mouse is strain dependent. In C57Bl/6 mice, the VH J558 family is expressed by more than 45% of the cells, while the expression of VH 7183, VH Q52, and VH 36-60 families together does not exceed 20%. In BALB/c mice, relative expression of VH J558 is lower than 35%, while the sum of the other three families reaches 25%. To assess which genetic loci control strain-specific VH gene family expression, we studied VH gene family usage in splenic B cell repertoires of different congenic strains of mice. Changes in major histocompatibility complex or immunoglobulin (Ig) K light chain genes did not modify VH gene family expression in adult mice. Differences at the IgH locus, however, modified VH gene family usage. In 1-d-old mice, the strain-specific VH gene family expression pattern is determined by the IgH haplotype. In adult mice, the VH gene family expression pattern of resting B cells is independent of the IgH locus and follows the genetic background of the congenic strain, while it is determined by the IgH haplotype among Ig-secreting spleen cells. In F1(B6 x BALB/c) mice, each of the two spleen B cell populations, sorted on the basis of mu heavy chain allotype expression, shows an independent VH gene family expression pattern, determined by the IgH locus. The implications of these results in the control of VH gene family expression, and in the selection of peripheral B cell repertoires are discussed.

Evidence of Pre-Diagnostic Monoclonality in Blood Obtained up to 6.4 Years Preceding Diagnosis of Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3082-3082
Author(s):  
Ola Landgren ◽  
Maher X. Albitar ◽  
Wanlong X. Ma ◽  
Fatima R. Abbasi ◽  
Richard B. Hayes ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Gene Family ◽  
B Cell ◽  
Suppressor Gene ◽  
Blood Draw ◽  
Color Flow ◽  
Mutation Status ◽  
Diagnostic Samples ◽  
Vh Gene ◽  
Clinical Records

Abstract Background: Monoclonal B-cell lymphocytosis (MBL) is reported in about 3% of the general adult population 65 yrs or older. Risk of progression from MBL to CLL requiring treatment has been estimated to about 1% per yr. For the first time we established the occurrence of preceding MBL using prospectively collected pre-diagnostic samples from CLL pts. Also, we tested the hypothesis that indolent (IgVH mutated) CLL occurs after MBL while aggressive (IgVH unmutated) CLL has an alternative route that develops rapidly or bypasses MBL. Methods: Using the population-based nationwide PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial (n>144,500 cancer-free adults), we identified 46 CLL pts with available baseline cryopreserved whole blood obtained 3 to 77 months prior to CLL diagnosis. Clinical information was retrieved from screening questionnaires and medical records. 10 healthy adult controls were included. 6-color flow cytometry (CD45/CD19/CD5/CD10/kappa/lambda) and reverse transcription/polymerase chain reaction (RT/PCR) for IgH gene were used to determine evidence of expression of monoclonal IgH gene family and to establish the VH gene mutation status. Direct sequencing without subcloning (for clonal cases) and with subcloning (for non-clonal cases) was used to determine mutation status. We sequenced exons 5, 6, 7, 8, and 9 of the p53 suppressor gene for mutations. Results: After exclusion of one subject with absent viable cells, we analyzed pre-diagnostic blood specimen from 45 CLL pts. CLL diagnosis was based on clinical criteria and confirmed by review of clinical records. Immunophenotyping data were available for 39 (87%) pts. The Rai CLL stage distribution was: 0 (n=26), 1 (n=9), 2 (n=2), 3 (n=1), missing/unclear (n=7). The mean time between pre-diagnostic blood draw and subsequent CLL diagnoses was 3 yrs. Using flow cytometry, sequencing, and PCR, we demonstrated evidence of monoclonality in 43/45 (96%) pre-diagnostic samples from CLL pts. Among individuals whose blood was obtained <3 yrs vs. >3 yrs prior CLL diagnosis, the proportion of pre-diagnostic monoclonality was 28/28 (100%) vs. 15/17 (88%), respectively; the proportion of IgVH mutated pre-diagnostic clones was the same in both groups: 23/28 (82%) vs. 14/17 (82%). The most frequently expressed VH gene family was VH3 (40%) followed by VH4 (29%), VH1 (9%), VH5 (9%), VH2 (7%), and VH6 (2%), with no expression of VH7 gene families. We found 2 pts with mutations in the p53 suppressor gene; one in exon7/M237K, and one in exon 6, P22 that is silent and has been reported as in some tumors and a polymorphism. One sample with unmutated IgVH appeared to have a deletion at p53 in both alleles. Immunophenotyping analyses for pre-diagnostic clones showed kappa n=27, lambda n=8, n=4 biclonal, and missing/indeterminate n=6 (kappa:lambda ratio >3:1). Comparisons of pre-diagnostic and diagnostic kappa/lambda status in the same persons showed 100% concordance. All negative controls lacked evidence of monoclonality. Conclusions: In this first prospective study examining pre-diagnostic blood obtained 3 to 77 months prior to CLL diagnosis, we found a monoclonal B-cell population in virtually all the persons; 82% were IgVH mutated. Our findings suggest that CLL is commonly preceded by the precursor condition MBL.

scholarly journals Murine V kappa gene expression does not follow the VH paradigm.

1989 ◽  
Vol 169 (5) ◽  
pp. 1859-1864 ◽  
Author(s):  
A Kaushik ◽  
D H Schulze ◽  
C Bona ◽  
G Kelsoe
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
B Lymphocytes ◽  
Gene Rearrangement ◽  
Gene Families ◽  
Genomic Complexity ◽  
Positional Bias ◽  
Vh Gene

V kappa gene family expression among LPS-reactive murine B lymphocytes, unlike that of VH gene families, is not proportional to genomic complexity, i.e., nonstoichiometric. Furthermore, no positional bias for the overexpression of J-proximal V kappa genes (V kappa 21) is observed among neonatal B lymphocytes. Yet, the V kappa 1 and V kappa 9 families located in the center of V kappa locus are preferentially used by neonatal B splenocytes. Thus, the mechanisms of V kappa gene rearrangement and expression appear to differ significantly from those controlling the VH locus.

scholarly journals VH gene family expression in mice with the xid defect.

1991 ◽  
Vol 174 (1) ◽  
pp. 45-51 ◽  
Author(s):  
S H Feng ◽  
K E Stein
Keyword(s):  
Gene Family ◽  
Gene Families ◽  
Gene Defect ◽  
X Chromosomes ◽  
Polysaccharide Antigens ◽  
Specific Antigens ◽  
Vh Gene ◽  
Vh Genes ◽  
Predominant Expression

Preferential use of particular VH gene families in the response to specific antigens has been demonstrated in several systems. The lack of responses to certain types of antigens, therefore, could be the result of deletion of or failure to express some VH genes. Because CBA/N mice, which carry the X-linked immunodeficiency (xid) gene defect, have been shown to be unresponsive to thymus-independent polysaccharide antigens, it was of interest to examine if this unresponsiveness could be accounted for by abnormal expression of particular VH gene families. Using in situ hybridization on B cell colonies, we determined the expression of nine VH gene families in CBA/CaHN females (genotypically normal), CBA/N males (xid) and females (xid), and (CBA/N x CBA/CaHN)F1 males (xid) and females (phenotypically normal). Our results indicate that VH gene family expression, including the S107 family, in CBA/N males and F1 males, is similar to that of CBA/CaHN and F1 females with predominant expression of J558, the largest gene family, in all individuals. Interestingly, CBA/N female mice, which carry two defective X chromosomes, as a group expressed significantly reduced levels of the J558 gene family, and as individuals showed variation in which family was predominantly expressed. We conclude that the unresponsiveness of mice with the xid defect to polysaccharide antigens can not attributed to a failure to express the nine VH gene families that we examined. Our findings do not support previous studies (Primi, D., and P.-A. Cazenave 1986. J. Exp. Med. 165:357), which found an absence of expression of the S107 family in xid mice.

Sign in / Sign up

Export Citation Format

Share Document