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Relative contribution of membrane‐bound complement regulatory proteins CD55, CD59, CD46, and soluble factor H to resistance of human B lymphoma cells to complement
Author(s) -
Ferreira Viviana P,
Pangburn Michael K.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1079.18
Subject(s) - cd59 , decay accelerating factor , cd46 , raji cell , factor h , complement system , complement dependent cytotoxicity , complement membrane attack complex , b cell lymphoma , cancer cell , antibody , cell , biology , lymphoma , cancer research , chemistry , immunology , monoclonal antibody , cancer , antibody dependent cell mediated cytotoxicity , biochemistry , genetics
The complement system uses a complex set of cell‐bound and plasma regulators to protect host cells from complement‐mediated lysis. Although membrane‐bound complement regulatory proteins (mCRPs) are known to protect cancer cell surfaces, thus interfering with anti‐cancer immunotherapy, the role of soluble factor H (fH) in their protection remains less clear. While large variations in expression of mCRPs (DAF, CD46, CD59, CR1) have been observed among tumors, fH, a key regulator of fluid phase and cell surface complement activity, is present at 500 μg/ml in blood. We have shown that recombinant C‐terminal domains 19–20 of fH (rH19–20) specifically block fH cell surface complement regulatory functions. In this study, rH19–20 + anti‐DAF and anti‐CD59 + anti‐DAF treatments similarly increased lysis of Raji lymphoma cells, compared to anti‐DAF alone. rH19–20 + anti‐DAF + Rituximab (an antibody treatment for B cell lymphoma) also increased lysis of cells vs anti‐DAF + Rituximab. Interestingly, blocking fH‐mediated cell surface protection and DAF resulted in the greatest increase in C3b and C9 deposition vs inhibiting any other combination of two regulators. The results highlight the importance of fH‐mediated cell surface protection, compared to mCRPs, and indicate that fH may be as important as mCRPs in its potential for posing an obstacle to antibody based cancer therapy. Support: NIH DK35081 and AHA 0735101N.