Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies, II

摘要: We have previously described complement-independent killing of human B lymphocytes by two IgM MoAbs derived from the VH4-34 (VH4.21) gene. Analysis 17 independently VH4-34-encoded shows that cell toxicity is not limited to MoAbs, but a general property shared subset As observed independent microscopy techniques, giant membrane pores were formed on target cells within 10–15 min exposure cytotoxic VH4-34-derived MoAbs. Toxicity individual MoAb correlated directly its binding intensity measured FACS, i.e. stronger greater killing. Sequence analysis showed VH region in germ-line or near configuration was necessary sufficient for binding. In addition, particular sequence motif enriched basic amino acids CDR3 may be required supplement reactivity mediated molecule. antibodies fulfil above requirements cold agglutinin activity towards i antigen cord erythrocytes. vivo, such anti-i/anti-B are rarely detected healthy adults, serum levels dramatically elevated selective pathological conditions, as systemic lupus erythematosus and infectious mononucleosis. This strict regulation related novel rapid mechanism demonstrated encoded single