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Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations.

Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL - J. Exp. Med. (1999)

Bottom Line: The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases.Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys.This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142, USA. fabienne_mackay@biogen.com

ABSTRACT
The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.

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Increased Ig, RF, and CIC levels in BAFF-Tg mice. (A) Reduced SDS-PAGE of sera from five control littermates and nine BAFF-Tg mice showing that BAFF increases IgG levels. For comparison, mouse IgG1 (MOPC-21) was included as a standard: loading per lane was 5 μg of MOPC-21 and 0.5 μl of the serum. The sharp band slightly below the Ig light chain is not an immunoglobulin and the IgM heavy chain comigrates with transferrin. ELISA-based analysis of total mouse Ig (B), RF (C), and CIC (D) in the sera of 19 control littermates (white bars) and 21 BAFF-Tg mice (black bars). The titer (log base 2) for RF is defined as the dilution of the sera giving an OD three times higher than that of background. The quantity of CIC is defined as the quantity of peroxidase-mouse antiperoxidase required to generate an OD equivalent to that obtained with the tested serum. The difference between control animals and BAFF-Tg mice was statistically significant (P < 0.001 in B and C, P < 0.003 in D).
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Figure 6: Increased Ig, RF, and CIC levels in BAFF-Tg mice. (A) Reduced SDS-PAGE of sera from five control littermates and nine BAFF-Tg mice showing that BAFF increases IgG levels. For comparison, mouse IgG1 (MOPC-21) was included as a standard: loading per lane was 5 μg of MOPC-21 and 0.5 μl of the serum. The sharp band slightly below the Ig light chain is not an immunoglobulin and the IgM heavy chain comigrates with transferrin. ELISA-based analysis of total mouse Ig (B), RF (C), and CIC (D) in the sera of 19 control littermates (white bars) and 21 BAFF-Tg mice (black bars). The titer (log base 2) for RF is defined as the dilution of the sera giving an OD three times higher than that of background. The quantity of CIC is defined as the quantity of peroxidase-mouse antiperoxidase required to generate an OD equivalent to that obtained with the tested serum. The difference between control animals and BAFF-Tg mice was statistically significant (P < 0.001 in B and C, P < 0.003 in D).

Mentions: The increased B cell compartment in BAFF-Tg mice suggested that the level of total Ig in the blood of these animals might also be increased. SDS-PAGE analysis of the serum showed that IgG levels were elevated in all BAFF-Tg mice, while the nontransgenic littermates displayed a normal pattern of serum proteins (Fig. 6 A). By comparison with an IgG1 standard antibody, the levels of IgG in a nontransgenic mouse were ∼5–8 mg/ml, and these levels increased to at least 50 mg/ml in some BAFF-Tg mice (quantification was done with underloaded gels). In normal mice, the light chain band is smeared due to the polyclonal nature of the Ig and on this basis the elevated Ig levels in BAFF-Tg mice were also polyclonal in nature. IgM levels were visibly increased in these mice, albeit not as much as IgG, and this band is seen as a smear on top of a transferrin band in this gel.


Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations.

Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL - J. Exp. Med. (1999)

Increased Ig, RF, and CIC levels in BAFF-Tg mice. (A) Reduced SDS-PAGE of sera from five control littermates and nine BAFF-Tg mice showing that BAFF increases IgG levels. For comparison, mouse IgG1 (MOPC-21) was included as a standard: loading per lane was 5 μg of MOPC-21 and 0.5 μl of the serum. The sharp band slightly below the Ig light chain is not an immunoglobulin and the IgM heavy chain comigrates with transferrin. ELISA-based analysis of total mouse Ig (B), RF (C), and CIC (D) in the sera of 19 control littermates (white bars) and 21 BAFF-Tg mice (black bars). The titer (log base 2) for RF is defined as the dilution of the sera giving an OD three times higher than that of background. The quantity of CIC is defined as the quantity of peroxidase-mouse antiperoxidase required to generate an OD equivalent to that obtained with the tested serum. The difference between control animals and BAFF-Tg mice was statistically significant (P < 0.001 in B and C, P < 0.003 in D).
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Related In: Results  -  Collection

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Figure 6: Increased Ig, RF, and CIC levels in BAFF-Tg mice. (A) Reduced SDS-PAGE of sera from five control littermates and nine BAFF-Tg mice showing that BAFF increases IgG levels. For comparison, mouse IgG1 (MOPC-21) was included as a standard: loading per lane was 5 μg of MOPC-21 and 0.5 μl of the serum. The sharp band slightly below the Ig light chain is not an immunoglobulin and the IgM heavy chain comigrates with transferrin. ELISA-based analysis of total mouse Ig (B), RF (C), and CIC (D) in the sera of 19 control littermates (white bars) and 21 BAFF-Tg mice (black bars). The titer (log base 2) for RF is defined as the dilution of the sera giving an OD three times higher than that of background. The quantity of CIC is defined as the quantity of peroxidase-mouse antiperoxidase required to generate an OD equivalent to that obtained with the tested serum. The difference between control animals and BAFF-Tg mice was statistically significant (P < 0.001 in B and C, P < 0.003 in D).
Mentions: The increased B cell compartment in BAFF-Tg mice suggested that the level of total Ig in the blood of these animals might also be increased. SDS-PAGE analysis of the serum showed that IgG levels were elevated in all BAFF-Tg mice, while the nontransgenic littermates displayed a normal pattern of serum proteins (Fig. 6 A). By comparison with an IgG1 standard antibody, the levels of IgG in a nontransgenic mouse were ∼5–8 mg/ml, and these levels increased to at least 50 mg/ml in some BAFF-Tg mice (quantification was done with underloaded gels). In normal mice, the light chain band is smeared due to the polyclonal nature of the Ig and on this basis the elevated Ig levels in BAFF-Tg mice were also polyclonal in nature. IgM levels were visibly increased in these mice, albeit not as much as IgG, and this band is seen as a smear on top of a transferrin band in this gel.

Bottom Line: The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases.Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys.This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142, USA. fabienne_mackay@biogen.com

ABSTRACT
The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.

Show MeSH
Related in: MedlinePlus