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VH gene family expression in mice with the xid defect
1Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Abstract:
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.
Insights
The X-linked immunodeficiency (xid) gene defect in mice does not cause unresponsiveness to polysaccharide antigens due to abnormal expression of VH gene families. This study examined nine VH gene families in xid mice, finding no significant differences in expression patterns.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Specific VH gene family usage is crucial for immune responses to various antigens.
- Mice with the X-linked immunodeficiency (xid) gene defect exhibit unresponsiveness to thymus-independent polysaccharide antigens.
- The underlying cause of this unresponsiveness in xid mice, specifically regarding VH gene expression, remains unclear.
Purpose of the Study:
- To investigate whether the unresponsiveness to polysaccharide antigens in xid mice is associated with abnormal expression of specific VH gene families.
- To compare VH gene family expression profiles between normal mice and mice with the xid defect.
Main Methods:
- Utilized in situ hybridization on B cell colonies to analyze the expression of nine VH gene families.
- Examined VH gene expression in genetically normal mice (CBA/CaHN females), xid mice (CBA/N males and females), and F1 hybrid mice (carrying the xid defect or phenotypically normal).
Main Results:
- VH gene family expression, including the S107 family, was found to be similar in xid and normal mice, with the J558 family being predominantly expressed across all groups.
- Interestingly, xid female mice (with two defective X chromosomes) showed reduced J558 gene family expression and individual variations in predominant VH gene family expression.
- The study did not find evidence supporting previous claims of S107 family expression absence in xid mice.
Conclusions:
- The unresponsiveness to polysaccharide antigens in mice with the xid defect cannot be attributed to a failure in expressing the nine examined VH gene families.
- These findings challenge previous research suggesting a link between S107 family expression and the xid defect.
- VH gene family expression patterns in xid mice are largely comparable to those in normal mice, indicating other mechanisms may underlie polysaccharide antigen unresponsiveness.