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.

scholarly journals Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice.

1990 ◽  
Vol 171 (3) ◽  
pp. 843-859 ◽  
Author(s):  
B A Malynn ◽  
G D Yancopoulos ◽  
J E Barth ◽  
C A Bona ◽  
F W Alt
Keyword(s):  
Gene Families ◽  
Relative Expression ◽  
Immunodeficient Mice ◽  
Regulatory Interactions ◽  
Adult Mice ◽  
Neonatal Liver ◽  
Vh Gene ◽  
Vh Genes ◽  
Adult Bone ◽  
Insight Into

We have previously demonstrated a dramatic preference for utilization of the most JH-proximal VH gene segments in the newborn liver versus adult spleen. We now examine in detail the relative expression of different VH gene families throughout ontogeny and in immunodeficient mice to gain insight into factors that cause the shift in VH usage. We find that the relative expression of VH gene families remains constant and biased throughout fetal and neonatal liver development. In addition, the primary VH repertoire expressed in neonatal spleen displays a similarly biased, position-dependent VH repertoire. The pattern of VH gene expression begins to change at 5-7 d postnatally and reaches the adult randomized pattern at approximately 2 wk of age. We also find biased expression of JH-proximal VH gene families in adult bone marrow and in spleens of adult leaky scid mice, suggesting that the spontaneously generated repertoire of adult mice is similar to that observed in neonates. Together, these data suggest that a position-dependent repertoire is generated in differentiating pre-B cells at all stages of ontogeny, at least in part, as a result of preferential rearrangement of proximal VH gene segments. Therefore, mechanisms subsequent to V gene rearrangement, such as regulatory interactions and antigen selection, must play a major role in normalizing the repertoire.

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

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.

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 Preferential use of the VH4 Ig gene family by diffuse large-cell lymphoma

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3072-3082 ◽  
Author(s):  
FJ Hsu ◽  
R Levy
Keyword(s):  
Gene Family ◽  
Cell Lymphoma ◽  
Variable Region ◽  
Gene Families ◽  
Large Cell ◽  
Germline Gene ◽  
Diffuse Large Cell Lymphoma ◽  
Vh Genes ◽  
Large Cell Lymphoma ◽  
Almost All

Abstract Ig heavy chain variable region (VH) genes expressed by human diffuse large-cell lymphoma (DLC) and follicular lymphoma (FL) were identified and analyzed with respect to germline gene families. In 67 cases of FL, VH region genes were expressed in a pattern similar to that of normal B cells, with a predominance of the large VH3 gene family being used. In contrast, of the 17 cases of DLC, there was an extremely biased use of VH genes. Of these DLC tumors, 88% expressed genes from the small VH4 gene family; and even among these tumors, there was a limited use of genes, with 11 cases producing Igs derived from the VH4.21 germline gene. Although most of the VH genes expressed by DLC tumor cells contained mutations with respect to their germline counterparts, almost all of these mutations occurred before the clonal expansion of the tumor. This contrasts with our previous findings of ongoing mutations in FL and represents a fundamental difference between these two malignancies. This preferential gene use implies an important role for the VH4 gene family, and specifically for VH4.21, in the genesis of DLC.

scholarly journals Eleven distinct VH gene families and additional patterns of sequence variation suggest a high degree of immunoglobulin gene complexity in a lower vertebrate, Xenopus laevis.

1990 ◽  
Vol 171 (5) ◽  
pp. 1721-1737 ◽  
Author(s):  
R N Haire ◽  
C T Amemiya ◽  
D Suzuki ◽  
G W Litman
Keyword(s):  
Xenopus Laevis ◽  
Gene Families ◽  
Sequence Difference ◽  
Immunoglobulin Gene ◽  
Vertebrate Species ◽  
Antibody Diversity ◽  
Lower Vertebrate ◽  
Nucleotide Sequence Difference ◽  
Vh Gene ◽  
Vh Genes

Lower vertebrate species, including Xenopus laevis, exhibit restricted antibody diversity relative to higher vertebrates. We have analyzed more than 180 VH gene-containing recombinant clones from an unamplified spleen cDNA library by selective sequencing of JH and CH positive clones following iterative hybridization screening with family-specific VH probes, 11 unique families of VH genes, each associated with a unique genomic Southern blot hybridization pattern, are described and compared. Considerable variation in the number of hybridizing components detected by each probe is evident. The nucleotide sequence difference between VH families is as great as, if not more than, that reported in other systems, including representatives of the mammalian, avian, and elasmobranch lineages. Some Xenopus Ig gene families encode alternative amino acids at positions that are otherwise invariant or very rarely substituted in known Igs. Furthermore, variations in complementarity determining region sequences among members of the same gene family and high degrees of DH and JH region complexity are described, suggesting that in at least this lower vertebrate species, the diversity of expressed Ig VH genes is not restricted.

scholarly journals Comparison of the fetal and adult functional B cell repertoires by analysis of VH gene family expression.

1988 ◽  
Vol 168 (2) ◽  
pp. 589-603 ◽  
Author(s):  
H D Jeong ◽  
J M Teale
Keyword(s):  
Gene Expression ◽  
In Situ Hybridization ◽  
B Cells ◽  
Gene Family ◽  
B Cell ◽  
Cell Lineage ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Vh Gene

The functional B cell repertoire in BALB/c mice was assessed at various stages in ontogeny. This was done by analyzing VH gene family expression using the sensitive technique of in situ hybridization. The B cell repertoire was probed with the mitogen, LPS, and the antigen DNP. DNP was chosen because B cells responsive to this hapten appear very early in ontogeny. The APCs that developed after stimulation with LPS or DNP were analyzed for VH gene expression by in situ hybridization of individual cells using radiolabeled VH gene family probes. The results indicated that VH gene expression in fetal B cells after stimulation was distinct from adult B cells in that there was a biased expression of D proximal families. The results indicated that this bias was associated with developmental age and not a given differentiation stage in the B cell lineage. In addition, stimulation of fetal B cells with DNP resulted in a large increase in expression of member(s) of VH 36-60, suggesting that the early appearance of DNP-responsive B cells is not strictly correlated with preferential rearrangement of D proximal families, VH 7183 and VH Q52. However, the results suggested that a large proportion of pre-B cells that preferentially rearrange D proximal families early in ontogeny become part of the functional developing repertoire.

scholarly journals Ig VH gene expression among human follicular lymphomas

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1561-1568 ◽  
Author(s):  
DW Bahler ◽  
MJ Campbell ◽  
S Hart ◽  
RA Miller ◽  
S Levy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Variable Region ◽  
Gene Families ◽  
Peripheral Blood Lymphocytes ◽  
Low Grade ◽  
Normal Peripheral Blood ◽  
Germline Genes ◽  
Vh Gene ◽  
Vh Genes ◽  
Follicular Lymphomas

Abstract Thirty-six randomly selected cases of low grade follicular lymphoma (FL) were analyzed for Ig heavy chain variable region (VH) gene expression. Assignment to one of the six human VH gene families (VH1 to VH6) was made with a polymerase chain reaction-based technique using family-specific leader primers. The frequency of VH family use in FL was found to be similar to that reported for normal peripheral blood lymphocytes and is therefore also roughly proportional to VH family size. To evaluate expression within an individual family, all of the lymphoma VH genes from the middle size VH4 family were sequenced and compared with previously published sequences. Of these eight lymphoma VH sequences, six were most closely related to just two of the 10 known functional VH4 germline genes. Nonrandom usage by FL of the JH3, JH4, and JH5 joining segments was also observed. Nucleotide sequences were also determined for 10 randomly selected lymphoma VH genes from the large VH3 family. With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire.

scholarly journals Genotypic analysis of B cell colonies by in situ hybridization. Stoichiometric expression of three VH families in adult C57BL/6 and BALB/c mice.

1987 ◽  
Vol 166 (1) ◽  
pp. 163-172 ◽  
Author(s):  
D H Schulze ◽  
G Kelsoe
Keyword(s):  
In Situ Hybridization ◽  
B Cell ◽  
Direct Evidence ◽  
Gene Families ◽  
Filter Paper Disc ◽  
Genotypic Analysis ◽  
Vh Gene ◽  
X 24 ◽  
Paper Disc

The filter paper disc method for cloning inducible lymphocytes was used to census the splenic B cell population of C57BL/6 and BALB/c mice for the expression of three VH gene-families, VH X-24, -Q52, and -J558. B cell colonies, arising from single founder lymphocytes, were identified by in situ hybridization with VH family- and C mu-specific cDNA probes. Some 6.7 X 10(4) C mu+ colonies were screened. Among C57BL/6- or BALB/c-derived colonies, approximately 3% were VH X-24+, approximately 19% were VH Q52+, and approximately 54% were VH J558+. These frequencies are consistent with a process of equiprobable expression for individual VH segments, and provide direct evidence that normal splenic B lymphocytes use a process of random genetic combinatorics to generate the antibody repertoire.

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