Absence of CD5 dramatically reduces progression of pulmonary inflammatory lesions in SHP-1 protein-tyrosine phosphatase-deficient 'viable motheaten' mice.
Mice homozygous for the viable motheaten (Hcph(me-v)) mutation are deficient in SHP-1 protein-tyrosine phosphatase, resulting in severe systemic autoimmunity and immune dysfunction. A high percentage of B-cells in viable motheaten mice express the cell surface glycoprotein CD5, in contrast to wild type mice that express CD5 on only a small percentage of B-cells. CD5(+) B-cells have been associated with autoantibody production. To determine the role of CD5 in the development of the inflammatory disease in me(v)/ me(v) mice, we created a stock of CD5(null)me(v)/ me(v) mice. The longevity of CD5(null)me(v)/ me(v) mice was increased 69% in comparison to me(v)/ me(v) mice on a similar (B6;129) background. The increased lifespan was associated with a marked reduction in pulmonary inflammation. Flow cytometry analysis of spleen cells from CD5(null)me(v)/ me(v) mice at 9-12 weeks of age revealed significant decreases in percentages of IgM/B220 double positive B-cells, Mac-1/Gr-1 double positive cells and CD4(+) T-cells compared with me(v)/ me(v) mice. CD5(null)me(v)/ me(v) mice also had significantly lower serum IgM levels in comparison to me(v)/ me(v) mice. Study of CD5(null)me(v)/ me(v) mice may provide further insight into the role of CD5 in cell signaling and may help explain the observed association of CD5(+) B-cells with autoimmune disease.
Joliat
Melissa J
MJ
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Lang
Pamela A
PA
Lyons
Bonnie L
BL
Burzenski
Lisa
L
Lynes
Michael A
MA
Yi
Taolin
T
Sundberg
John P
JP
Shultz
Leonard D
LD
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007136:Immunoglobulins / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins; D008136:Longevity; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D011014:Pneumonia / Q000201:enzymology / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D018956:CD5 Antigens; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse