scholarly journals Vaccination in PADs

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 626
Author(s):  
Cinzia Milito ◽  
Valentina Soccodato ◽  
Giulia Collalti ◽  
Alison Lanciarotta ◽  
Ilaria Bertozzi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Function ◽  
European Medicines Agency ◽  
Normal Numbers ◽  
Specific Data ◽  
Inactivated Vaccines ◽  
Hyper Igm ◽  
Deficient Vector ◽  
Common Variable

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; specific antibody deficiency with normal Ig concentrations and normal numbers of B cells and transient hypogammaglobulinemia of infancy. The role of vaccination in PADs is recognized as therapeutic, diagnostic and prognostic and may be used in patients with residual B-cell function to provide humoral immunity to specific infective agents. According to their content and mechanisms, vaccines are grouped as live attenuated, inactivated (conjugated, polysaccharide), mRNA or replication-deficient vector vaccines. Vaccination may be unsafe or less effective when using certain vaccines and in specific types of immunodeficiency. Inactivated vaccines can be administered in PAD patients even if they could not generate a protective response; live attenuated vaccines are not recommended in major antibody deficiencies. From December 2020, European Medicines Agency (EMA) approved vaccines against COVID-19 infection: according to ESID advises, those vaccinations are recommended in patients with PADs. No specific data are available on safety and efficacy in PAD patients.

Essential Roles for Mef2c in Lymphoid Commitment and B-Cell Function.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 377-377
Author(s):  
Sandra Stehling-Sun ◽  
Rebecca Jimenez ◽  
Andrew Hu ◽  
Fernando D. Camargo
Keyword(s):  
B Cells ◽  
B Cell ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Cell Function ◽  
Physiological Role ◽  
Erythroid Differentiation ◽  
Hematopoietic Stem ◽  
Interleukin 7

Abstract MEF2 transcription factors are well-established regulators of muscle development. Recently, work in murine models has identified one of these factors, Mef2c, as an important regulator in the pathogenesis and the development of acute myeloid leukemia (AML). However, little is know about the molecular mechanism and physiological role of Mef2c in hematopoiesis. Using conditional gene ablation, we have discovered an unexpected role for MEF2c in hematopoietic stem cells (HSCs), where it is required for pan-lymphoid commitment. Competitive repopulation experiments using Mef2c-null HSCs deleted by means of the Mx1-Cre/poly(IC) approach, revealed completely normal monocytic, granulocytic and erythroid differentiation capacities by mutant cells. Generation and renewal of myeloid progenitors and HSCs was also normal. However, contribution to lymphoid lineages (T-cells, B-cells and natural killer cells) was dramatically reduced. Mef2c-deleted HSCs were able to generate lymphoid primed multipotent progenitors (LMPPs) and expressed normal levels of Flt-3 and the master lymphoid regulator ikaros. However, expression of the interleukin-7 receptor (IL-7R) and the number of phenotypically defined common lymphoid progenitors (CLPs) were substantially reduced. We have found two conserved Mef2c-binding sites in the promoter of the Il-7R gene, indicating that Mef2c could directly regulate Il-7R transcription. This and other potential molecular mechanisms of Mef2c-mediated lymphoid commitment will be discussed. We have also studied the effects of lineage-specific deletion of Mef2c in both myeloid and lymphoid populations. Whereas deletion in myelomonocytic cells using the LysM-Cre strain resulted in no anomalies, B-cell specific ablation with the CD19-Cre line revealed major phenotypical and functional abnormalities. CD19-Cre:Mef2cf/f mice show impaired germinal center formation and reduced antibody production in response to T-cell dependent antigens. In addition Mef2c-null mature B-cells fail to express the mature marker CD23, the low affinity receptor for IgE, which we show is a direct transcriptional target. As a consequence of CD23 reduction, CD19-Cre:Mef2cf/f mice have increased IgE production, thus indicating a potential role of Mef2c in allergic disease. Our work here sheds new light on the molecular mechanisms of lymphopoiesis and identifies MEF2 factors as critical hematopoietic transcriptional regulators.

The role of toll-like receptors in B-cell development and immunopathogenesis of common variable immunodeficiency

2015 ◽  
Vol 12 (2) ◽  
pp. 195-207 ◽  
Author(s):  
Laleh Sharifi ◽  
Abbas Mirshafiey ◽  
Nima Rezaei ◽  
Gholamreza Azizi ◽  
Kabir Magaji Hamid ◽  
...  
Keyword(s):  
B Cell ◽  
Common Variable Immunodeficiency ◽  
Cell Development ◽  
B Cell Development ◽  
Toll Like Receptors ◽  
Common Variable

scholarly journals An overview of CD19 in COVID-19: Insights from Primary Immunodeficiencies and B cell depleting therapies

2020 ◽  
Author(s):  
Pulukool Sandhya ◽  
Abhinav Jain ◽  
Geeta Govindaraj
Keyword(s):  
B Cell ◽  
Cell Depletion ◽  
Biological Processes ◽  
B Cell Depletion ◽  
Pathogenic Role ◽  
Factors Associated ◽  
Global Pandemic ◽  
Systemic Autoimmunity ◽  
Common Variable

The evolution of COVID-19 as a global pandemic and emerging evidence from cohorts of patients have provided an immense opportunity to understand biological processes pertinent to development of the disease. The immune system is central to the development of characteristic hyperinflammation. In an attempt to understand the role of humoral immunity in COVID-19, reports encompassing patients with primary immunodeficiency (PID)(13 patients) and on B cell depletion therapies(39 patients) who had concurrent COVID-19 were reviewed. In PIDs, patients with common variable immunodeficiency had worse outcomes than patients with agammaglobulinemia. Among the patients on B cell depletion therapy, heterogenous outcome was seen. As a group, patients with multiple sclerosis had better outcomes as compared to patients with systemic autoimmunity. Further, increasing reports of autoimmunity and autoinflammatory diseases occurring in temporal relation to COVID-19 is also evidence for the pathogenic role played by B cells. B cell depletion in the setting of COVID-19 may not be harmful in all patients and in fact may be protective in some scenarios. Identification of risk factors associated with a worse outcome in patients on B cell therapy could provide a rationale for individualised management.

Defects in B-cell function and metabolism in uremia: Role of parathyroid hormone

2001 ◽  
Vol 59 (s78) ◽  
pp. 186-189 ◽  
Author(s):  
Miroslaw Smogorzewski ◽  
Shaul G. Massry
Keyword(s):  
Parathyroid Hormone ◽  
B Cell ◽  
Cell Function ◽  
B Cell Function

scholarly journals Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1887-1894 ◽  
Author(s):  
E Bolotin ◽  
M Smogorzewska ◽  
S Smith ◽  
M Widmer ◽  
K Weinberg
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
T Lymphocytes ◽  
B Cell ◽  
Cell Function ◽  
Normal Numbers ◽  
B Cell Function ◽  
Interleukin 7 ◽  
Immature Thymocytes

Abstract Bone marrow transplantation (BMT) is followed by a period of profound immune deficiency, during which new T lymphocytes are generated from either stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces proliferation and differentiation of immature thymocytes. We examined whether the in vivo administration of IL-7 to mice receiving BMT would alter thymic reconstitution. Lethally irradiated C57BL/6 mice received syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18 post-BMT. At day 28, BMT recipients that had not received IL-7 had profound thymic hypoplasia (< 5% of normal), with relative increases in the numbers of immature thymocytes, decreased numbers of mature peripheral (splenic) T lymphocytes, and severely impaired T- and B-cell function. In contrast, transplanted mice treated with IL-7 had normalization of thymic cellularity, with normal proportions of thymic subsets and T-cell receptor beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T lymphocytes, and improved antigen- specific T- and B-cell function. In the BMT-IL-7 mice, there was an eightfold increase in the number of immature CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that restoration of thymic cellularity was due to enhanced proliferation of immature thymic progenitors. Similar effects following IL-7 administration were also observed when donor bone marrow was depleted of mature T lymphocytes, indicating that IL-7 administration affected immature hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT, and may be useful in preventing post-BMT immune deficiency.

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.

scholarly journals Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1887-1894 ◽  
Author(s):  
E Bolotin ◽  
M Smogorzewska ◽  
S Smith ◽  
M Widmer ◽  
K Weinberg
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
T Lymphocytes ◽  
B Cell ◽  
Cell Function ◽  
Normal Numbers ◽  
B Cell Function ◽  
Interleukin 7 ◽  
Immature Thymocytes

Bone marrow transplantation (BMT) is followed by a period of profound immune deficiency, during which new T lymphocytes are generated from either stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces proliferation and differentiation of immature thymocytes. We examined whether the in vivo administration of IL-7 to mice receiving BMT would alter thymic reconstitution. Lethally irradiated C57BL/6 mice received syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18 post-BMT. At day 28, BMT recipients that had not received IL-7 had profound thymic hypoplasia (< 5% of normal), with relative increases in the numbers of immature thymocytes, decreased numbers of mature peripheral (splenic) T lymphocytes, and severely impaired T- and B-cell function. In contrast, transplanted mice treated with IL-7 had normalization of thymic cellularity, with normal proportions of thymic subsets and T-cell receptor beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T lymphocytes, and improved antigen- specific T- and B-cell function. In the BMT-IL-7 mice, there was an eightfold increase in the number of immature CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that restoration of thymic cellularity was due to enhanced proliferation of immature thymic progenitors. Similar effects following IL-7 administration were also observed when donor bone marrow was depleted of mature T lymphocytes, indicating that IL-7 administration affected immature hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT, and may be useful in preventing post-BMT immune deficiency.

scholarly journals Gut microbiota influence B cell function in a TLR5-dependent manner

2019 ◽  
Author(s):  
Sha Li ◽  
William A. Walters ◽  
Benoit Chassaing ◽  
Benyue Zhang ◽  
Qiaojuan Shi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Hypervariable Region ◽  
Slight Reduction ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Low Levels ◽  
Deficient Mice

AbstractToll-like receptor (TLR) 5-deficient mice display aberrantly low levels of flagellin-specific antibodies (Flic-IgA) secreted into the gut, combined with excess bacterial flagellin in the gut, and together these attributes define microbiome dysbiosis (T5-dysbiosis). How TLR5 signaling deficiency results in T5-dysbiosis is unclear. Here, we address the role of B cells in T-dysbiosis. We observed that B cells do not express TLR5, and that B cell transplantation from TLR5−/− mouse donors into B-cell deficient mice resulted in a slight reduction in Flic-IgA levels compared to B-cells from WT donors. Bone marrow transplants from WT and TLR5−/− donors into recipients of both genotypes confirmed that TLR5 signaling by non-hematopoietic cells is required for T5-dysbiosis. We observed TLR5 deficiency was associated with an expanded population of IgA+ B cells. TLR5−/− mice tended to have higher richness for the IgA gene hypervariable region (CDR3 gene) variants. Transplantation of microbiomes from TLR5−/− and WT microbiomes donors into germfree mice resulted in a higher proportion of IgA-secreting B cells, and higher overall fecal IgA and anti-Flic IgA for TLR5−/− microbiome recipients. This observation indicated that the TLR5−/− mouse microbiome elicits an anti-flagellin antibody response that requires TLR5 signaling. Together these results indicate that TLR5 signaling on epithelial cells influences B cell populations and antibody repertoire.

Role of Rapamycin-Induced Autophagy in Pancreatic B-Cell Function

2012 ◽  
Vol 94 (10S) ◽  
pp. 730-731
Author(s):  
M. Tanemura ◽  
H. Nagano ◽  
Y. Ohmura ◽  
Y. Iwagami ◽  
H. Wada ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Function ◽  
Pancreatic B Cell ◽  
B Cell Function

Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay

2014 ◽  
Vol 0 (0) ◽  
Author(s):  
Jeffrey M. Faint ◽  
Supratik Basu ◽  
David Sutton ◽  
Paul J. Showell ◽  
Philip A. Kalra ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Cell Function ◽  
Clinical Samples ◽  
B Cell Activation ◽  
Free Light Chains ◽  
Serum Free Light Chain ◽  
Assay Time ◽  
Polyclonal Serum

AbstractElevated polyclonal serum free light chain (FLC) levels have been associated with increased mortality and disease activity in many conditions. Currently, polyclonal FLC quantification requires summation of individual FLCκ and FLCλ assays. Here we present a single assay for combined FLC (cFLC, Combylite™) which reduces assay time and eliminates potential imprecision errors incurred by summating FLC assays (ΣFLC).Sheep FLCκ- and FLCλ-specific antibodies were conjugated to latex microparticles to quantify FLCκ and FLCλ in a single assay. Combylite results were compared to ΣFLC (FreelitecFLC and ΣFLC results were highly concordant (Passing-Bablok equation y=0.98x–1.59 mg/L, RcFLC values obtained using Combylite were comparable to ΣFLC results over a wide concentration range, were elevated in diseases characterised by B cell activation and were associated with increased mortality in a haematological referral population. These observations indicate the Combylite assay has value for investigating the role of B cell activation in disparate disease groups and could be considered as a surrogate indication of B cell function.

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