We have identified a rare healthy FcγRIIIB (CD16B)-null donor completely lacking FCGR3B RNA and protein expression and dissected the role of the different neutrophil Fcγ receptors in the response to therapeutic anti-CD20 monoclonal antibodies. We observed that polymorphonuclear neutrophils (PMNs) from FcγRIIIB wild-type (WT) individuals or the null donor were more effectively activated by chronic lymphocytic leukemia (CLL) B-cell targets opsonized with glycoengineered anti-CD20 antibodies compared with fully core-fucosylated anti-CD20 antibodies, suggesting the presence and role of FcγRIIIA (CD16A) on PMNs. Indeed, we demonstrated by reverse-transcription polymerase chain reaction, flow cytometry, and western blot analysis that PMNs from FcγRIIIB WT donors and the null individual express low levels of FcγRIIIA on their surfaces.
View Article and Find Full Text PDFAutoantibodies to intracellular antigens form a large family of immunoglobulins directed to a variety of ubiquitously expressed intracellular molecules, including numerous enzymes, some ribonucleoproteins and double-stranded DNA. These anti-self antibodies have been found to be selectively expressed in sera of patients with several systemic (non-organ-specific) autoimmune diseases, such as systemic sclerosis (SSc), SLE, mixed connective tissue disease, Sjögren's syndrome and idiopathic myopathies. Despite their important diagnostic and prognostic value and their utility in assessing disease activity, little is known about the molecular mechanisms involved in their generation and role in autoimmune diseases nor is it known why particular autoantibodies are preferentially expressed in certain diseases.
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