The B cell superantigen-like interaction of intravenous immunoglobin (IVIG) with Fab fragments of V(H) 3-23 and 3-30/3-30.5 germline gene origin cloned from a patient with Kawasaki disease is enhanced after IVIG therapy.
The etiology of Kawasaki disease (KD) is still unknown. Therefore, the diagnosis relies on clinical criteria only. Although a specific therapy for KD is not available, coronary complications can be significantly reduced with the help of intravenous immunoglobulin (IVIG) therapy. It is not clear how IVIG interacts with the immune system. Previously, we selected a large number of IgG and IgM Fab fragments specifically reacting with IVIG molecules by phage display and antiidiotypic panning from three patients with autoimmune thrombocytopenia, a patient with lupus, and a healthy individual. Sequencing revealed that the favored V(H) germline gene segments of these IVIG-bound Fabs were 3-23 or 3-30/3-30.5, the most frequently rearranged V(H) genes among human B cells. The binding pattern suggested a B cell superantigen-like, specific interaction of an IVIG subset with B cells that present B cell receptors derived from these two germline genes. The aim of the current study was to investigate whether treatment with IVIG influences this restricted interaction. Therefore we cloned and selected Fab fragments from a patient with KD before and after IVIG therapy. A favored selection of antibodies derived from both the 3-23 and the 3-30/3-30.5 germline gene segments as before was observed. Importantly, the reactivity with IVIG was significantly higher for clones from the library prepared after the IVIG treatment, providing the first in vivo functional evidence that a subset of IVIG may selectively activate B cells of this germline origin. This mechanism may add to the therapeutic effect of IVIG in the treatment of KD.
Leucht
S
S
Laboratory of Molecular Biology, Children's Hospital, Otto Heubner Centrum, Charité, Humboldt-University, 10117 Berlin, Germany.
Uttenreuther-Fischer
M M
MM
Gaedicke
G
G
Fischer
P
P
D001402:B-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology / Q000628:therapy*; D019151:Peptide Library; D018089:Superantigens / Q000276:immunology*
D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D016756:Immunoglobulins, Intravenous; D019151:Peptide Library; D018089:Superantigens