The A48RI expressed on the ABPC48 and UPC10 beta 2----6 fructosan-binding myeloma proteins is a conformational antigenic determinant encoded by V genes deriving from the VHX24 and VK10 families. In the preimmune repertoire the clones using VHX24 genes rarely express A48 idiotopes, clearly demonstrating that this regulatory idiotope is a minor or silent idiotope. Furthermore, these same VHX24-utilizing preimmune clones are frequently associated with the VK1 gene family which is highly represented in the neonatal and adult repertoires. The clonal expansion occurring subsequent to neonatal injection of minute amounts of anti-Id antibodies leads to selective expansion of A48Id+ clones associated with class switching. Few somatic mutations are observed in preimmune clones, or in those expanded by anti-Id antibodies. The fact that few mutations were observed in the IgG1 clones obtained from animals injected with anti-A48Id antibodies after birth indicates that, in contrast to antigen-induced class-switching, the anti-Id-induced switching is not associated with a highly active mutational process. In contrast to the preimmune clones, or those expanded by anti-Id (in the absence of antigenic stimulation) in which VHX24 is associated with VK regions deriving from various gene families, the clones expanded by anti-Id and fructan resemble A48 by using VHX24 and VK10 genes. Few apparent mutations were also observed in these IgM or IgG3 clones expressing A48 idiotopes. The A48 RI can be expressed on clones producing antibodies specific for various self and foreign antigens, and encoded by V genes deriving from various VH and VK families. These results indicate that key contacting residues bearing A48 conformational idiotypic determinants can be made up by various VH-VK combinations. A comparison of the VH and VL sequences of A48 RI+ mAbs showed that many of the observed somatic mutations could be correlated to decreased IDA10 binding. This comparison allowed identification of specific idiotope-determining regions of VH and VK which could represent contacting residues with anti-idiotypic antibodies. The contributions of these regions to the expression of the A48Id was tested by generating a transfectoma antibody expressing the rearranged VHJ558 gene of the ricin 45 hybridoma and the VK10-Ars-a gene of the 36-65 hybridoma. This transfectoma antibody expresses the idiotope recognized by IDA10 and confirms the conformational nature of this idiotope. There are three amino acid residues shared by VHX24 and VHJ558 antibodies expressing the A48 RI which are important for its expression.(ABSTRACT TRUNCATED AT 400 WORDS)
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http://dx.doi.org/10.1111/j.1600-065x.1989.tb00032.x | DOI Listing |
Front Immunol
February 2023
Pediatric Immunology, Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
B cell maturation and immunoglobulin (Ig) repertoire selection are governed by expression of a functional B cell receptor (BCR). Naïve B cells co-express their BCR as IgM and IgD isotype. However, the role of the additionally expressed IgD on naïve B cells is not known.
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December 2021
Laboratory for Environmental and Life Sciences, University of Nova Gorica, 5000 Nova Gorica, Slovenia.
C-reactive protein (CRP) is an inflammation biomarker that should be quantified accurately during infections and healing processes. Nanobodies are good candidates to replace conventional antibodies in immunodiagnostics due to their inexpensive production, simple engineering, and the possibility to obtain higher binder density on capture surfaces. Starting from the same pre-immune library, we compared the selection output resulting from two independent panning strategies, one exclusively exploiting the phage display and another in which a first round of phage display was followed by a second round of yeast display.
View Article and Find Full Text PDFEur J Immunol
March 2021
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
Enterobacteriaceae are a large family of Gram-negative bacteria that includes both commensals and opportunistic pathogens. The latter can cause severe nosocomial infections, with outbreaks of multi-antibiotics resistant strains, thus being a major public health threat. In this study, we report that Enterobacteriaceae-reactive memory Th cells were highly enriched in a CCR6 CXCR3 Th1*/17 cell subset and produced IFN-γ, IL-17A, and IL-22.
View Article and Find Full Text PDFScience
July 2020
Department of Immunobiology, Yale University, New Haven, CT 06511, USA.
Restricted V(D)J recombination during fetal development was postulated to limit antibody repertoire breadth and prevent autoimmunity. However, newborn serum contains abundant autoantibodies, suggesting that B cell tolerance during gestation is not yet fully established. To investigate this apparent paradox, we evaluated the reactivities of more than 450 antibodies cloned from single B cells from human fetal liver, bone marrow, and spleen.
View Article and Find Full Text PDFBMC Med Res Methodol
March 2020
CHU Ste-Justine Research Center, Montréal, H3T1C5, Canada.
Background: With the growth in use of biotherapic drugs in various medical fields, the occurrence of anti-drug antibodies represents nowadays a serious issue. This immune response against a drug can be due either to pre-existing antibodies or to the novel production of antibodies from B-cell clones by a fraction of the exposed subjects. Identifying genetic markers associated with the immunogenicity of biotherapeutic drugs may provide new opportunities for risk stratification before the introduction of the drug.
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