Israel Medical Association Journal

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or “homing receptors.” Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL[1] patients.

Methods: Expression of adhesion molecules belonging to different families was studied in CD19-positive cells isolated from the blood of 42 patients by dual color flow cytometry. The families included: immunoglobulin superfamily (CD54, CD58), integrin family (β1, β2 and β3 chains, CD11a, CD11c CD49d), selectin family (L-selectin), and lymphocyte homing receptor family (CD44).

Results: The average percentage of leukemic cells expressing CD11c in the 23 patients with stage II(S) was 25.7 compared with 13.2% in the 14 patients with stage 0 disease (P = 0.047). The average percentage of leukemic cells expressing CD44 in patients with stage II(S) was 90.5 compared with 77.2% in patients with stage 0 (P = 0.007) and 80% in patients with stages 0 and I together (n=19, P = 0.008). Other adhesion molecules tested did not show a statistically significance difference in expression between the different disease stages.

Conclusions: The higher expression of CD44 and CD11c in cells of CLL patients with predominantly splenic manifestations may account for the tendency of their lymphocytes to home to the spleen.