Selection of apoptotic cell specific human antibodies from adult bone marrow.
Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC)-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.
School of Medicine, New York University, New York, New York, United States of America.
Caroline
C
Grönwall
Laboratory of Virology and Infectious Disease, Rockefeller University, New York, New York, United States of America.
Edgar D
ED
Charles
University of Oxford, Oxford, United Kingdom.
Lynn B
LB
Dustin
Department of Cancer Biology and Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida, United States of America.
Christoph
C
Rader
School of Medicine, New York University, New York, New York, United States of America.
Gregg J
GJ
Silverman
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism; D000918:Antibody Specificity; D017209:Apoptosis; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D010767:Phosphorylcholine / Q000378:metabolism*; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D010767:Phosphorylcholine