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A chronic model of arthritis supported by a strain-specific periarticular lymph node in BALB/c mice.

Baddack U, Hartmann S, Bang H, Grobe J, Loddenkemper C, Lipp M, Müller G - Nat Commun (2013)

Bottom Line: However, BALB/c mice generate significantly higher titres of anticollagen and anticitrullinated peptide antibodies, show a stronger progressive joint destruction, and in the chronic phase the disease spreads between joints.Concomitant to the observation of a more severe pathology, we discovered a previously undescribed small periarticular lymph node in close proximity to the knee joint of BALB/c mice, which acts as the primary draining lymph node for the synovial cavity.Our model more closely reflects the pathology of rheumatoid arthritis than classical models of arthritis and is hence particularly suitable for further studies of disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Max-Delbrück-Center of Molecular Medicine, Department of Tumor Genetics and Immunogenetics, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.

ABSTRACT
Current animal models of arthritis only partially reflect the complexity of rheumatoid arthritis and typically lack either chronicity or autoantibody formation. Here we describe a model that combines features of antigen-induced arthritis and collagen-induced arthritis, which can be efficiently induced in BALB/c and C57BL/6 mice. However, BALB/c mice generate significantly higher titres of anticollagen and anticitrullinated peptide antibodies, show a stronger progressive joint destruction, and in the chronic phase the disease spreads between joints. Concomitant to the observation of a more severe pathology, we discovered a previously undescribed small periarticular lymph node in close proximity to the knee joint of BALB/c mice, which acts as the primary draining lymph node for the synovial cavity. Our model more closely reflects the pathology of rheumatoid arthritis than classical models of arthritis and is hence particularly suitable for further studies of disease pathogenesis.

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Generation of antigen-specific plasma cells in the GCs of the paLN.Consecutive cryosections of the paLN from BALB/c mice with chronic arthritis were stained in red for binding of the irrelevant protein ovalbumin (a, left panel) or biotinylated mBSA (a, right panel). The paLN was stained for plasma cells with a biotinylated anti-CD138 antibody (b, left panel) or biotinylated mBSA (b, right). Sections are representative for three independent experiments. Magnification X200.
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f4: Generation of antigen-specific plasma cells in the GCs of the paLN.Consecutive cryosections of the paLN from BALB/c mice with chronic arthritis were stained in red for binding of the irrelevant protein ovalbumin (a, left panel) or biotinylated mBSA (a, right panel). The paLN was stained for plasma cells with a biotinylated anti-CD138 antibody (b, left panel) or biotinylated mBSA (b, right). Sections are representative for three independent experiments. Magnification X200.

Mentions: Having shown that active GCs are formed in the paLN after the onset of arthritis, we wanted to further explore their involvement in the autoimmune response. In arthritic mice we were able to detect cells specific for mBSA in the paLN (Fig. 4a). All the more, we could detect CD138-positive plasma cells that co-localize with the mBSA-specific cells within the GCs of the paLN (Fig. 4b). Hence, within these GCs B cells can differentiate into mature plasma cells expressing antibodies directed against a local (auto)antigen. When comparing the paLN directly with the popliteal lymph node it became obvious that only few single plasma cells were present in the popliteal lymph node, whereas the paLN harboured large areas of CD138+ plasma cells within the B cell zones.


A chronic model of arthritis supported by a strain-specific periarticular lymph node in BALB/c mice.

Baddack U, Hartmann S, Bang H, Grobe J, Loddenkemper C, Lipp M, Müller G - Nat Commun (2013)

Generation of antigen-specific plasma cells in the GCs of the paLN.Consecutive cryosections of the paLN from BALB/c mice with chronic arthritis were stained in red for binding of the irrelevant protein ovalbumin (a, left panel) or biotinylated mBSA (a, right panel). The paLN was stained for plasma cells with a biotinylated anti-CD138 antibody (b, left panel) or biotinylated mBSA (b, right). Sections are representative for three independent experiments. Magnification X200.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3644064&req=5

f4: Generation of antigen-specific plasma cells in the GCs of the paLN.Consecutive cryosections of the paLN from BALB/c mice with chronic arthritis were stained in red for binding of the irrelevant protein ovalbumin (a, left panel) or biotinylated mBSA (a, right panel). The paLN was stained for plasma cells with a biotinylated anti-CD138 antibody (b, left panel) or biotinylated mBSA (b, right). Sections are representative for three independent experiments. Magnification X200.
Mentions: Having shown that active GCs are formed in the paLN after the onset of arthritis, we wanted to further explore their involvement in the autoimmune response. In arthritic mice we were able to detect cells specific for mBSA in the paLN (Fig. 4a). All the more, we could detect CD138-positive plasma cells that co-localize with the mBSA-specific cells within the GCs of the paLN (Fig. 4b). Hence, within these GCs B cells can differentiate into mature plasma cells expressing antibodies directed against a local (auto)antigen. When comparing the paLN directly with the popliteal lymph node it became obvious that only few single plasma cells were present in the popliteal lymph node, whereas the paLN harboured large areas of CD138+ plasma cells within the B cell zones.

Bottom Line: However, BALB/c mice generate significantly higher titres of anticollagen and anticitrullinated peptide antibodies, show a stronger progressive joint destruction, and in the chronic phase the disease spreads between joints.Concomitant to the observation of a more severe pathology, we discovered a previously undescribed small periarticular lymph node in close proximity to the knee joint of BALB/c mice, which acts as the primary draining lymph node for the synovial cavity.Our model more closely reflects the pathology of rheumatoid arthritis than classical models of arthritis and is hence particularly suitable for further studies of disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Max-Delbrück-Center of Molecular Medicine, Department of Tumor Genetics and Immunogenetics, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.

ABSTRACT
Current animal models of arthritis only partially reflect the complexity of rheumatoid arthritis and typically lack either chronicity or autoantibody formation. Here we describe a model that combines features of antigen-induced arthritis and collagen-induced arthritis, which can be efficiently induced in BALB/c and C57BL/6 mice. However, BALB/c mice generate significantly higher titres of anticollagen and anticitrullinated peptide antibodies, show a stronger progressive joint destruction, and in the chronic phase the disease spreads between joints. Concomitant to the observation of a more severe pathology, we discovered a previously undescribed small periarticular lymph node in close proximity to the knee joint of BALB/c mice, which acts as the primary draining lymph node for the synovial cavity. Our model more closely reflects the pathology of rheumatoid arthritis than classical models of arthritis and is hence particularly suitable for further studies of disease pathogenesis.

Show MeSH
Related in: MedlinePlus