Hyper-IgM immunodeficiency syndrome: Influence of lymphokines onin vitro maturation of peripheral B cells

Purpose of the Studies. Hyper-IgM immunodeficiency is characterized by recurrent bacterial infections, normal or elevated IgM, and markedly decreased IgG, IgA, and IgE. Previous research suggested that the T cells of these patients are defective in their ability to help B cells make functional antibody. CD40 ligand (CD4OL) is a membrane glycoprotein on activated T helper cells and binds the CD40 molecule expressed on B cells, and induces proliferation and immunoglobulin class switching (in conjunction with IL-4). The gene for the CD4OL has been mapped to position q26.3-q27.1 on chromosome X (same as the Hyper-IgM gene and the area of isotype switching). Several research groups sought to determine if the immunodeficiency in Hyper-IgM patients is due to defective CD4OL. Findings. The five papers listed above document the work of different research groups that simultaneously found abnormalities in the CD4OL gene in a total of 16 patients with X-linked Hyper-IgM syndrome. Different mutations of the CD4OL gene have been discovered, including point mutations, deletions, and nonsense sequences. Mutant version of CD4OL taken from Hyper IgM patients were unable to "help" B cells in vitro. Thus, deficient CD40/CD40L interactions between B and T cells results in severely impaired immunity. Restricted CD40L gene expression to T cells may ultimately allow gene therapy as treatment. Reviewers' Comments. A concise editorial by Jean Marx entitled "Cell Communication Failure Leads to Immune Disorder" describes this landmark research and accompanies the Spriggs article in the February 12th issue of Science (pp. 896-897). This discovery may not only lead to treatment of this disorder, but also modification of other less favorable immune responses.

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CD40 LIGAND MUTATIONS IN X-LINKED IMMUNODEFICIENCY WITH HYPER-IgM

PEDIATRICS ◽

10.1542/peds.94.2.280d ◽

1994 ◽

Vol 94 (2) ◽

pp. 280-280

Author(s):

Arden Levy ◽

Andrew Liu

Keyword(s):

T Cells ◽

B Cells ◽

Bacterial Infections ◽

Point Mutations ◽

Cell Communication ◽

Cd40 Ligand ◽

Research Groups ◽

Immune Disorder ◽

Hyper Igm

Purpose of the Studies. Hyper-IgM immunodeficiency is characterized by recurrent bacterial infections, normal or elevated IgM, and markedly decreased IgG, IgA, and IgE. Previous research suggested that the T cells of these patients are defective in their ability to help B cells make functional antibody. CD40 ligand (CD4OL) is a membrane glycoprotein on activated T helper cells and binds the CD40 molecule expressed on B cells, and induces proliferation and immunoglobulin class switching (in conjunction with IL-4). The gene for the CD4OL has been mapped to position q26.3-q27.1 on chromosome X (same as the Hyper-IgM gene and the area of isotype switching). Several research groups sought to determine if the immunodeficiency in Hyper-IgM patients is due to defective CD4OL. Findings. The five papers listed above document the work of different research groups that simultaneously found abnormalities in the CD4OL gene in a total of 16 patients with X-linked Hyper-IgM syndrome. Different mutations of the CD4OL gene have been discovered, including point mutations, deletions, and nonsense sequences. Mutant version of CD4OL taken from Hyper IgM patients were unable to "help" B cells in vitro. Thus, deficient CD40/CD40L interactions between B and T cells results in severely impaired immunity. Restricted CD40L gene expression to T cells may ultimately allow gene therapy as treatment. Reviewers' Comments. A concise editorial by Jean Marx entitled "Cell Communication Failure Leads to Immune Disorder" describes this landmark research and accompanies the Spriggs article in the February 12th issue of Science (pp. 896-897). This discovery may not only lead to treatment of this disorder, but also modification of other less favorable immune responses.

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The generation of the human mab RabD4 specific to the rabies virus glycoprotein and characterization thereof

Доклады Академии наук ◽

10.31857/s0869-56524853370-373 ◽

2019 ◽

Vol 485 (3) ◽

pp. 370-373

Author(s):

Е. N. Ilina ◽

E. V. Solopova ◽

Т. К. Aliev ◽

М. V. Larina ◽

D. S. Balabashin ◽

...

Keyword(s):

B Cells ◽

Rabies Virus ◽

Binding Activity ◽

Antigen Binding ◽

Rabies Virus Glycoprotein ◽

Neutralizing Activity ◽

Virus Glycoprotein ◽

Peripheral B Cells

We generated a novel human neutralizing human mAb RabD4 against rabies virus glycoprotein using in vitro stimulation human peripheral B cells produced from immunized donor. It was revealed that the human mAb RabD4 demonstrated high antigen-binding activity and virus-neutralizing activity in the FAVN test with the CVS-11 rabies virus.

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The CD154/CD40 Interaction Required for Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated by Upregulation of the CD80/CD86 Costimulatory Molecules

Journal of Virology ◽

10.1128/jvi.76.24.13106-13110.2002 ◽

2002 ◽

Vol 76 (24) ◽

pp. 13106-13110 ◽

Cited By ~ 13

Author(s):

Kathy A. Green ◽

W. James Cook ◽

Arlene H. Sharpe ◽

William R. Green

Keyword(s):

Monoclonal Antibody ◽

B Cells ◽

Molecular Interactions ◽

T And B Cells ◽

Antibody Treatment ◽

Monoclonal Antibody Treatment ◽

Murine Aids ◽

Cd40 Expression ◽

Immunodeficiency Syndrome

ABSTRACT C57BL/6 (B6) mice infected with LP-BM5 retroviruses develop disease, including an immunodeficiency similar to AIDS. This disease, murine AIDS (MAIDS), is inhibited by in vivo anti-CD154 monoclonal antibody treatment. The similar levels of insusceptibility of CD40−/− and CD154−/− B6 mice indicate that CD154/CD40 molecular interactions are required for MAIDS. CD4+ T and B cells, respectively, provide the CD154 and CD40 expression needed for MAIDS induction. Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86−/− B6 mice develop MAIDS after LP-BM5 infection.

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Treatment with TNFα blockers induces phenotypical and functional aberrations in peripheral B cells

Clinical Immunology ◽

10.1016/j.clim.2011.01.012 ◽

2011 ◽

Vol 140 (1) ◽

pp. 8-17 ◽

Cited By ~ 12

Author(s):

Maria P. Karampetsou ◽

Andrew P. Andonopoulos ◽

Stamatis-Nick C. Liossis

Keyword(s):

B Cells ◽

Peripheral B Cells

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Analysis of peripheral B cells and autoantibodies against the anti-nicotinic acetylcholine receptor derived from patients with myasthenia gravis using single-cell manipulation tools

PLoS ONE ◽

10.1371/journal.pone.0185976 ◽

2017 ◽

Vol 12 (10) ◽

pp. e0185976 ◽

Cited By ~ 9

Author(s):

Tomohiro Makino ◽

Ryuichi Nakamura ◽

Maki Terakawa ◽

Satoshi Muneoka ◽

Kazuhiro Nagahira ◽

...

Keyword(s):

B Cells ◽

Myasthenia Gravis ◽

Single Cell ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Cell Manipulation ◽

Nicotinic Acetylcholine ◽

Single Cell Manipulation ◽

Peripheral B Cells

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Enzyme and Immunohistochemistry of Follicular Hyperplasia in AIDS-related Lymphadenopathy

The International Journal of Biological Markers ◽

10.1177/172460088700200206 ◽

1987 ◽

Vol 2 (2) ◽

pp. 87-94

Author(s):

Antonino Carbone ◽

Alessandro Poletti ◽

Riccardo Manconi ◽

Marzia Cozzi ◽

Sandro Sulfaro ◽

...

Keyword(s):

T Cells ◽

Alkaline Phosphatase ◽

B Cells ◽

Polyclonal Antibodies ◽

Lymph Node Biopsy ◽

Drug Abusers ◽

Double Labelling ◽

Mantle Zone ◽

Follicular Hyperplasia ◽

Immunodeficiency Syndrome

We used a panel of monoclonal and polyclonal antibodies to analyze frozen and paraffin-embedded lymph node biopsy specimens from 25 intravenous drug abusers (IVDA) with acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy histologically characterized by follicular hyperplasia. Our aim was to obtain diagnostic clues to this commonly occurring pattern. Double-labelling immunohistological studies were also performed on selected frozen sections and 13 plastic-embedded specimens were tested by a number of enzyme reactions. Consistent features in IVDA included abnormally high numbers of intrafollicular T-cells, positive for acid phosphatase and beta-glucuronidase, most of which had Leu-2a-positive phenotype; a marked reduction or loss of mantle zone B-cells (positive for surface IgD-IgM and alkaline phosphatase); and disarray of the network of follicular dendritic reticulum cells (DRCs), as revealed with DRC-1 and anti-S-100 protein antibodies or with reaction for 5'-nucleotidase. When present, distinctive intrafollicular clusters of Leu-2a-positive T-cells and mantle zone B-cells were nearly always associated with areas lacking DRCs in some patients. The intrafollicular hypervascularity invariably found in IVDA proved to be of a true capillary nature, as demonstrated by alkaline phosphatase, 5'-nucleotidase, and ATPase reactions. In control tissues, all showing absence of Leu-2a-positive intrafollicular T-cells, most of the above individual changes could be detected, although they were occasional, mild, and never associated within the same follicle. By contrast, combined immunohistological and enzyme histochemical findings in IVDA indicated that in most follicles such changes were marked and very often associated within the same follicle in each case. It can be concluded that on the basis of a combined analysis of lymphoid and non-lymphoid follicular constituents, the histological changes of AIDS-related lymphadenopathy with follicular hyperplastic pattern are further defined and corroborated.

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