scholarly journals Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production

2006 ◽  
Vol 203 (6) ◽  
pp. 1567-1578 ◽  
Author(s):  
Gregory C. Ippolito ◽  
Robert L. Schelonka ◽  
Michael Zemlin ◽  
Ivaylo I. Ivanov ◽  
Ryoki Kobayashi ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Production ◽  
Cell Function ◽  
Cell Development ◽  
B Cell Development ◽  
Antigen Binding Site ◽  
Cell Numbers ◽  
Charged Amino Acids ◽  
Antibody Titers

Tyrosine and glycine constitute 40% of complementarity determining region 3 of the immunoglobulin heavy chain (CDR-H3), the center of the classic antigen-binding site. To assess the role of DH RF1-encoded tyrosine and glycine in regulating CDR-H3 content and potentially influencing B cell function, we created mice limited to a single DH encoding asparagine, histidine, and arginines in RF1. Tyrosine and glycine content in CDR-H3 was halved. Bone marrow and spleen mature B cell and peritoneal cavity B-1 cell numbers were also halved, whereas marginal zone B cell numbers increased. Serum immunoglobulin G subclass levels and antibody titers to T-dependent and T-independent antigens all declined. Thus, violation of the conserved preference for tyrosine and glycine in DH RF1 alters CDR-H3 content and impairs B cell development and antibody production.

The Roles of Bursal Nonapeptide (BP9) on AIV Vaccine Immune Response in Chick Immunization and on Avian Immature B Cell

2019 ◽  
Vol 26 (12) ◽  
pp. 940-948
Author(s):  
Yang Zheng ◽  
Man M. Zong ◽  
Bo Y. Chen ◽  
Xiao H. Zhou ◽  
Zi N. Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Antibody Production ◽  
Cell Development ◽  
B Cell Development ◽  
Mrna Levels ◽  
Biological Processes ◽  
Gene Expressions ◽  
Antibody Titers ◽  
Dt40 Cells

Background: Bursa of Fabricius plays the vital functions on B cell development and antibody production in poultry. The bursal-derived peptide plays the essential roles on avian immature B cell development. Objectives: Here we explored the functions of the recently reported bursal nonapeptide (BP9) on the antibody production and the molecular basis of BP9 on avian immature B cell. Methods: Chicken were twice immunized with Avian Influenza Virus (AIV) inactivated vaccine plus with BP9 at three dosages, respectively. On two weeks after the second immunization, sera samples were collected from all experimental groups to measure AIV-specific Agglutination Inhibition (HI) antibody titers. Also, on 7th day after the second immunization, spleen lymphocytes were isolated from the immunized chicken to detect the lymphocyte viabilities. DT40 cells were treated with BP9 from 0.02 to 2 μg/mL for 4 and 20h to detect sIgM mRNA levels, and total RNAs from BP9-treated DT40 cells were collected to investigate the gene expression profiles of DT40 cells, and to analyze the enriched pathways and functional biological processes. Finally, nine gene expressions were validated with quantitative PCR (qPCR). Results: Our investigation proved the strong regulatory roles of BP9 on AIV-specific HI antibody titers and lymphocyte viabilities. BP9 promoted sIgM mRNA levels in DT40 cells, and upregulated 598 gene expressions and downregulated 395 gene expressions in DT40 cells with 0.2μg/mL BP9 treatment. Moreover, our findings verified the significantly enriched six pathways and various the biological functional processes of BP9 on avian immature B cell. Also, we found eight signaling pathways in the enriched biological processes of BP9-treated DT40 cells, and the expressions of nine selected genes with qPCR were identical to that of microarray data. Conclusion: BP9 promoted the antibody production in the 21-old-day chicken immunization, and stimulated the sIgM expression in DT40 cells. Furthermore, we analyzed the gene expression profile and immune-related biological processes of DT40 cells treated with BP9, which provided some new insights into the mechanism on immature B cell development, and provided important references for adjuvant development on vaccine improvement and clinical application.

Genetic Control of DH Reading Frame and Its Effect on B-Cell Development and Antigen-Specifc Antibody Production

2010 ◽  
Vol 30 (4) ◽  
pp. 327-344 ◽  
Author(s):  
Harry W. Schroeder, Jr. ◽  
Michael Zemlin ◽  
Mohamed Khass ◽  
Huan H. Nguyen ◽  
Robert L. Schelonka
Keyword(s):  
B Cell ◽  
Genetic Control ◽  
Antibody Production ◽  
Cell Development ◽  
B Cell Development ◽  
Reading Frame

scholarly journals In and Out of the Bursa—The Role of CXCR4 in Chicken B Cell Development

2020 ◽  
Vol 11 ◽  
Author(s):  
Nandor Nagy ◽  
Florian Busalt ◽  
Viktoria Halasy ◽  
Marina Kohn ◽  
Stefan Schmieder ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Development ◽  
B Cell Development

scholarly journals Lsh/HELLS is required for B lymphocyte development and immunoglobulin class switch recombination

2020 ◽  
Vol 117 (33) ◽  
pp. 20100-20108
Author(s):  
Yafeng He ◽  
Jianke Ren ◽  
Xiaoping Xu ◽  
Kai Ni ◽  
Andrew Schwader ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
B Cell ◽  
Marrow Transplantation ◽  
Class Switch Recombination ◽  
B Cell Development ◽  
Hematopoietic Cell ◽  
Cell Numbers ◽  
Class Switch

Mutation of HELLS (Helicase, Lymphoid-Specific)/Lsh in human DNA causes a severe immunodeficiency syndrome, but the nature of the defect remains unknown. We assessed here the role of Lsh in hematopoiesis using conditional Lsh knockout mice with expression of Mx1 or Vav Cre-recombinase. Bone marrow transplantation studies revealed that Lsh depletion in hematopoietic stem cells severely reduced B cell numbers and impaired B cell development in a hematopoietic cell-autonomous manner. Lsh-deficient mice without bone marrow transplantation exhibited lower Ig levels in vivo compared to controls despite normal peripheral B cell numbers. Purified B lymphocytes proliferated normally but produced less immunoglobulins in response to in vitro stimulation, indicating a reduced capacity to undergo class switch recombination (CSR). Analysis of germline transcripts, examination of double-stranded breaks using biotin-labeling DNA break assay, and End-seq analysis indicated that the initiation of the recombination process was unscathed. In contrast, digestion–circularization PCR analysis and high-throughput sequencing analyses of CSR junctions and a chromosomal break repair assay indicated an impaired ability of the canonical end-joining pathway in Lsh-deficient B cells. Our data suggest a hematopoietic cell-intrinsic role of Lsh in B cell development and in CSR providing a potential target for immunodeficiency therapy.

scholarly journals Mutations of the Igβ gene cause agammaglobulinemia in man

2007 ◽  
Vol 204 (9) ◽  
pp. 2047-2051 ◽  
Author(s):  
Simona Ferrari ◽  
Vassilios Lougaris ◽  
Stefano Caraffi ◽  
Roberta Zuntini ◽  
Jianying Yang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Transmembrane Protein ◽  
Serum Levels ◽  
Cell Development ◽  
B Cell Development ◽  
Surrogate Light Chain ◽  
Human B Cell ◽  
Homozygous Nonsense Mutation

Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, μ heavy chain, surrogate light chain, Igα, and B cell linker have been found in 85–90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igβ, which is a transmembrane protein that associates with Igα as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igβ is no longer able to associate with Igα, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igβ for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igβ can cause agammaglobulinemia in man.

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