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Effects of breeding environments on generation and activation of autoreactive B-1 cells in anti-red blood cell autoantibody transgenic mice.

Murakami M, Nakajima K, Yamazaki K, Muraguchi T, Serikawa T, Honjo T - J. Exp. Med. (1997)

Bottom Line: In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut.In germ-free conditions, few peritoneal B-1 cells were detected, while a significant number of peritoneal B-1 cells existed in specific pathogen-free conditions.These results clearly showed that bacterial infections are responsible for both the expansion of B-1 cells and the onset of the autoimmune disease in these Tg mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Chemistry, Kyoto University Faculty of Medicine, Sakyo-ku Yoshida, Japan.

ABSTRACT
In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut. About one-half of the auto Ab Tg mice suffer from autoimmune hemolytic anemia (AIHA) in the conventional condition. Oral administration of lipopolysaccharides activates B-1 cells and induces autoimmune symptoms in the Tg mice, suggesting that the autoimmune disease in anti-RBC autoAb Tg mice is triggered by infections. To examine the association of bacterial infections with the generation of B-1 cells and the occurrence of the autoimmune disease, we analyzed anti-RBC autoAb Tg mice bred in germ-free and specific pathogen-free conditions. In germ-free conditions, few peritoneal B-1 cells were detected, while a significant number of peritoneal B-1 cells existed in specific pathogen-free conditions. In both conditions, no mice suffered from AIHA. However, when these Tg mice were transferred to the conventional condition or injected with lipopolysaccharide, peritoneal B-1 cells expanded and some of these mice suffered from AIHA. These results clearly showed that bacterial infections are responsible for both the expansion of B-1 cells and the onset of the autoimmune disease in these Tg mice.

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The number of peritoneal B-1 cells in anti-RBC autoAb Tg  mice depends on breeding conditions. Peritoneal cells of 8- to 16-wk-old  anti-RBC autoAb Tg mice bred in different environments were examined by flow cytometric analysis with anti-IgM and anti-B220 or antiMac-1 Abs. GF/ConV: anti-RBC autoAb Tg mice bred in the GF condition were transferred to the conventional condition (ConV ) and kept  there for 4–6 wk before examination. Percentages of cell numbers in each  quadrant are indicated.
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Figure 1: The number of peritoneal B-1 cells in anti-RBC autoAb Tg mice depends on breeding conditions. Peritoneal cells of 8- to 16-wk-old anti-RBC autoAb Tg mice bred in different environments were examined by flow cytometric analysis with anti-IgM and anti-B220 or antiMac-1 Abs. GF/ConV: anti-RBC autoAb Tg mice bred in the GF condition were transferred to the conventional condition (ConV ) and kept there for 4–6 wk before examination. Percentages of cell numbers in each quadrant are indicated.

Mentions: In our previous studies, we showed that conventional B cells are almost completely deleted in this Tg model and that B-1 cells, which survive in the peritoneal cavity, are responsible for the autoimmune disease (12–15). To examine the effects of environmental conditions on generation of B-1 cells, we collected lymphocytes from peritoneal cavities, spleens, and bone marrows of Tg mice, and analyzed them by flow cytometry after staining with fluorescence-congugated mAbs. In spleens and bone marrows, B cells, including B-1 cells and conventional B cells, were hardly detected in Tg mice bred in the SPF and GF conditions as well as in the conventional condition (data not shown). By contrast, the numbers of B-1 cells in the peritoneal cavity of Tg mice are different depending on environmental conditions. The peritoneal cavity of GF Tg mice contained no or few B cells, whereas SPF Tg mice had a lesser but significant number of B-1 cells (B220+, IgM+, Mac-1+) as compared with Tg mice bred in the conventional condition (Fig. 1). Moreover, when GF Tg mice were transferred to the conventional condition, a small but significant number of B-1 cells appeared in the peritonal cavity (Fig. 1).


Effects of breeding environments on generation and activation of autoreactive B-1 cells in anti-red blood cell autoantibody transgenic mice.

Murakami M, Nakajima K, Yamazaki K, Muraguchi T, Serikawa T, Honjo T - J. Exp. Med. (1997)

The number of peritoneal B-1 cells in anti-RBC autoAb Tg  mice depends on breeding conditions. Peritoneal cells of 8- to 16-wk-old  anti-RBC autoAb Tg mice bred in different environments were examined by flow cytometric analysis with anti-IgM and anti-B220 or antiMac-1 Abs. GF/ConV: anti-RBC autoAb Tg mice bred in the GF condition were transferred to the conventional condition (ConV ) and kept  there for 4–6 wk before examination. Percentages of cell numbers in each  quadrant are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196146&req=5

Figure 1: The number of peritoneal B-1 cells in anti-RBC autoAb Tg mice depends on breeding conditions. Peritoneal cells of 8- to 16-wk-old anti-RBC autoAb Tg mice bred in different environments were examined by flow cytometric analysis with anti-IgM and anti-B220 or antiMac-1 Abs. GF/ConV: anti-RBC autoAb Tg mice bred in the GF condition were transferred to the conventional condition (ConV ) and kept there for 4–6 wk before examination. Percentages of cell numbers in each quadrant are indicated.
Mentions: In our previous studies, we showed that conventional B cells are almost completely deleted in this Tg model and that B-1 cells, which survive in the peritoneal cavity, are responsible for the autoimmune disease (12–15). To examine the effects of environmental conditions on generation of B-1 cells, we collected lymphocytes from peritoneal cavities, spleens, and bone marrows of Tg mice, and analyzed them by flow cytometry after staining with fluorescence-congugated mAbs. In spleens and bone marrows, B cells, including B-1 cells and conventional B cells, were hardly detected in Tg mice bred in the SPF and GF conditions as well as in the conventional condition (data not shown). By contrast, the numbers of B-1 cells in the peritoneal cavity of Tg mice are different depending on environmental conditions. The peritoneal cavity of GF Tg mice contained no or few B cells, whereas SPF Tg mice had a lesser but significant number of B-1 cells (B220+, IgM+, Mac-1+) as compared with Tg mice bred in the conventional condition (Fig. 1). Moreover, when GF Tg mice were transferred to the conventional condition, a small but significant number of B-1 cells appeared in the peritonal cavity (Fig. 1).

Bottom Line: In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut.In germ-free conditions, few peritoneal B-1 cells were detected, while a significant number of peritoneal B-1 cells existed in specific pathogen-free conditions.These results clearly showed that bacterial infections are responsible for both the expansion of B-1 cells and the onset of the autoimmune disease in these Tg mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Chemistry, Kyoto University Faculty of Medicine, Sakyo-ku Yoshida, Japan.

ABSTRACT
In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut. About one-half of the auto Ab Tg mice suffer from autoimmune hemolytic anemia (AIHA) in the conventional condition. Oral administration of lipopolysaccharides activates B-1 cells and induces autoimmune symptoms in the Tg mice, suggesting that the autoimmune disease in anti-RBC autoAb Tg mice is triggered by infections. To examine the association of bacterial infections with the generation of B-1 cells and the occurrence of the autoimmune disease, we analyzed anti-RBC autoAb Tg mice bred in germ-free and specific pathogen-free conditions. In germ-free conditions, few peritoneal B-1 cells were detected, while a significant number of peritoneal B-1 cells existed in specific pathogen-free conditions. In both conditions, no mice suffered from AIHA. However, when these Tg mice were transferred to the conventional condition or injected with lipopolysaccharide, peritoneal B-1 cells expanded and some of these mice suffered from AIHA. These results clearly showed that bacterial infections are responsible for both the expansion of B-1 cells and the onset of the autoimmune disease in these Tg mice.

Show MeSH
Related in: MedlinePlus