scholarly journals Targeted Inactivation of the Tetraspanin CD37 Impairs T-Cell-Dependent B-Cell Response under Suboptimal Costimulatory Conditions

2000 ◽  
Vol 20 (15) ◽  
pp. 5363-5369 ◽  
Author(s):  
Klaus-Peter Knobeloch ◽  
Mark D. Wright ◽  
Adrian F. Ochsenbein ◽  
Oliver Liesenfeld ◽  
Jürgen Löhler ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Viral Infections ◽  
Cell Interactions ◽  
Antibody Responses ◽  
Cellular Activation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Targeted Inactivation ◽  
Deficient Mice

ABSTRACT CD37 is a membrane protein of the tetraspanin superfamily, which includes CD9, CD53, CD63, CD81, and CD82. Many of these molecules are expressed on leukocytes and have been implicated in signal transduction, cell-cell interactions, and cellular activation and development. We generated and analyzed mice deficient for CD37. Despite the high expression of CD37 on cells of the immune system, no changes in development and cellular composition of lymphoid organs were observed in mice lacking CD37. Analyses of humoral immune responses revealed a reduced level of immunoglobulin G1 (IgG1) in the sera of nonimmunized mice and an alteration of responses to T-cell-dependent antigens. Antibody responses to model antigen administered in the absence of adjuvant and to viral infections were generally poor in CD37-deficient mice. These poor antibody responses could be overcome by the immunization of antigen together with adjuvant. These results suggest a role for CD37 in T-cell–B-cell interactions which manifests itself under suboptimal costimulatory conditions.

Mice Deficient for the Ecto-Nicotinamide Adenine Dinucleotide Glycohydrolase CD38 Exhibit Altered Humoral Immune Responses

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1324-1333 ◽  
Author(s):  
Debra A. Cockayne ◽  
Tony Muchamuel ◽  
J. Christopher Grimaldi ◽  
Hélène Muller-Steffner ◽  
Troy D. Randall ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Antibody Responses ◽  
Nicotinamide Adenine ◽  
Humoral Immune ◽  
Nad Glycohydrolase ◽  
Humoral Immune Responses

Abstract CD38 is a membrane-associated ecto-nicotinamide adenine dinucleotide (NAD+) glycohydrolase that is expressed on multiple hematopoietic cells. The extracellular domain of CD38 can mediate the catalysis of NAD+ to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing second messenger, adenosine diphosphoribose (ADPR), and nicotinamide. In addition to its enzymatic properties, murine CD38 has been shown to act as a B-cell coreceptor capable of modulating signals through the B-cell antigen receptor. To investigate the in vivo physiological function(s) of this novel class of ectoenzyme we generated mice carrying a null mutation in the CD38 gene. CD38−/− mice showed a complete loss of tissue-associated NAD+ glycohydrolase activity, showing that the classical NAD+ glycohydrolases and CD38 are likely identical. Although murine CD38 is expressed on hematopoietic stem cells as well as on committed progenitors, we show that CD38 is not required for hematopoiesis or lymphopoiesis. However, CD38−/− mice did exhibit marked deficiencies in antibody responses to T-cell–dependent protein antigens and augmented antibody responses to at least one T-cell–independent type 2 polysaccharide antigen. These data suggest that CD38 may play an important role in vivo in regulating humoral immune responses. © 1998 by The American Society of Hematology.

scholarly journals Role of Interleukin-23-Dependent Antifungal Immune Responses in Dendritic Cell-Vaccinated Mice

2011 ◽  
Vol 79 (9) ◽  
pp. 3778-3783 ◽  
Author(s):  
Mingquan Zheng ◽  
Rekha R. Rapaka ◽  
Amy C. Yu ◽  
Judd E. Shellito ◽  
Jay K. Kolls
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Recombinant Adenovirus ◽  
Cd40 Ligand ◽  
Antibody Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Interleukin 23 ◽  
Deficient Mice

ABSTRACTCD40 ligand (CD40L) transduction of antigen-pulsed dendritic cells (DCs) can result in antigen-specific humoral immune responses even in CD4+T-cell-depleted settings. Here, we show that CD40L transduction of DCs results in the induction of interleukin-12p40 (IL-12p40), IL-12p70, and IL-23. Using DCs that were deficient in IL-12p40, IL-12p35, or IL-23p19, we show that these molecules are dispensable for primary IgG1 responses toPneumocystis, but IgG2c was dependent on IL-12p40 and IL-23p19 but not IL-12p35. Antigen-specific recall responses in CD4-deficient mice were critically dependent on IL-12p40 and IL-23p19 expression in DCs and were not affected by the lack of IL-12p35. To confirm that this defect in recall was due to IL-23, transduction of IL-12p40−/−DCs with a recombinant adenovirus expressing functional IL-23 restored recall responses in DC-vaccinated CD4-deficient mice. These data show that DC-produced IL-23 is critical for vaccine-induced antigen-specific IgG2c and recall antibody responses in the setting of CD4+T-cell depletion.

Mice Deficient for the Ecto-Nicotinamide Adenine Dinucleotide Glycohydrolase CD38 Exhibit Altered Humoral Immune Responses

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1324-1333 ◽  
Author(s):  
Debra A. Cockayne ◽  
Tony Muchamuel ◽  
J. Christopher Grimaldi ◽  
Hélène Muller-Steffner ◽  
Troy D. Randall ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Antibody Responses ◽  
Nicotinamide Adenine ◽  
Humoral Immune ◽  
Nad Glycohydrolase ◽  
Humoral Immune Responses

CD38 is a membrane-associated ecto-nicotinamide adenine dinucleotide (NAD+) glycohydrolase that is expressed on multiple hematopoietic cells. The extracellular domain of CD38 can mediate the catalysis of NAD+ to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing second messenger, adenosine diphosphoribose (ADPR), and nicotinamide. In addition to its enzymatic properties, murine CD38 has been shown to act as a B-cell coreceptor capable of modulating signals through the B-cell antigen receptor. To investigate the in vivo physiological function(s) of this novel class of ectoenzyme we generated mice carrying a null mutation in the CD38 gene. CD38−/− mice showed a complete loss of tissue-associated NAD+ glycohydrolase activity, showing that the classical NAD+ glycohydrolases and CD38 are likely identical. Although murine CD38 is expressed on hematopoietic stem cells as well as on committed progenitors, we show that CD38 is not required for hematopoiesis or lymphopoiesis. However, CD38−/− mice did exhibit marked deficiencies in antibody responses to T-cell–dependent protein antigens and augmented antibody responses to at least one T-cell–independent type 2 polysaccharide antigen. These data suggest that CD38 may play an important role in vivo in regulating humoral immune responses. © 1998 by The American Society of Hematology.

scholarly journals TRAF6 Is Required for Generation of the B-1a B Cell Compartment as well as T Cell-Dependent and -Independent Humoral Immune Responses

PLoS ONE ◽  
2009 ◽  
Vol 4 (3) ◽  
pp. e4736 ◽  
Author(s):  
Takashi Kobayashi ◽  
Tae Soo Kim ◽  
Anand Jacob ◽  
Matthew C. Walsh ◽  
Yuho Kadono ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Cell Compartment ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals B cell ADAM17 controls T cell independent humoral immune responses through regulation of TACI and CD138

2020 ◽  
Vol 522 (2) ◽  
pp. 442-447
Author(s):  
Joseph C. Lownik ◽  
Jessica L. Wimberly ◽  
Leila Takahashi-Ruiz ◽  
Rebecca K. Martin
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses

2006 ◽  
Vol 203 (3) ◽  
pp. 599-606 ◽  
Author(s):  
Silvia B. Boscardin ◽  
Julius C.R. Hafalla ◽  
Revati F. Masilamani ◽  
Alice O. Kamphorst ◽  
Henry A. Zebroski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymphoid Organs ◽  
Antibody Responses ◽  
Carrier Protein ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Maturation Stimulus ◽  
T Cell Help

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.

scholarly journals Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus

2006 ◽  
Vol 203 (3) ◽  
pp. 529-539 ◽  
Author(s):  
Rika Draenert ◽  
Todd M. Allen ◽  
Yang Liu ◽  
Terri Wrin ◽  
Colombe Chappey ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Viral Infections ◽  
Immune Escape ◽  
Monozygotic Twins ◽  
T Cell Response ◽  
Envelope Gene ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cell Counts

The predictability of virus–host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.

scholarly journals Humoral immune responses in CD40 ligand-deficient mice.

1994 ◽  
Vol 180 (5) ◽  
pp. 1889-1900 ◽  
Author(s):  
B R Renshaw ◽  
W C Fanslow ◽  
R J Armitage ◽  
K A Campbell ◽  
D Liggitt ◽  
...  
Keyword(s):  
T Cell ◽  
Humoral Immunity ◽  
Bacterial Infections ◽  
Keyhole Limpet Hemocyanin ◽  
Cd40 Ligand ◽  
Antibody Responses ◽  
Humoral Immune ◽  
T Cell Subpopulations ◽  
Deficient Mice

Individuals with X-linked hyper-IgM syndrome fail to express functional CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses to opportunistic bacterial infections. To address the role of CD40L in humoral immunity, we created, through homologous recombination, mice deficient in CD40L expression. These mice exhibited no gross developmental deficiencies or health abnormalities and contained normal percentages of B and T cell subpopulations. CD40L-deficient mice did display selective deficiencies in humoral immunity; basal serum isotype levels were significantly lower than observed in normal mice, and IgE was undetectable. Furthermore, the CD40L-deficient mice failed to mount secondary antigen-specific responses to immunization with a thymus-dependent antigen, trinitrophenol-conjugated keyhole limpet hemocyanin (TNP-KLH). By contrast, the CD40L-deficient mice produced antigen-specific antibody of all isotypes except IgE in response to the thymus-independent antigen, DNP-Ficoll. These results underscore the requirement of CD40L for T cell-dependent antibody responses. Moreover, Ig class switching to isotypes other than IgE can occur in vivo in the absence of CD40L, supporting the notion that alternative B cell signaling pathways regulate responses to thymus-independent antigens.

scholarly journals Impaired Immune Responses and B-Cell Proliferation in Mice Lacking the Id3 Gene

1999 ◽  
Vol 19 (9) ◽  
pp. 5969-5980 ◽  
Author(s):  
Lihua Pan ◽  
Shinichi Sato ◽  
Joshua P. Frederick ◽  
Xiao-Hong Sun ◽  
Yuan Zhuang
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Cell Cycle Progression ◽  
Cross Linking ◽  
Cycle Progression ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Deficient Mice

ABSTRACT B-lymphocyte activation and proliferation induced by the B-cell receptor (BCR) signals are important steps in the initiation of humoral immune responses. How the BCR signals are translated by nuclear transcription factors into cell cycle progression is poorly understood.Id3 is an immediate-early gene responding to growth and mitogenic signals in many cell types including B cells. The primary function of the Id3 protein has been defined as that of inhibitor of basic-helix-loop-helix (bHLH) transcription factors. The interaction between Id3 and bHLH proteins, many of which are essential for cellular differentiation, has been proposed as a key regulatory event leading to cellular proliferation instead of differentiation. To further investigate the role of Id3 in tissue and embryo development and the mechanism of Id3-mediated growth regulation, we generated and analyzedId3-deficient mice. While these mice display no overt abnormality in tissue and embryo development, their humoral immunity is compromised. The amounts of immunoglobulins produced inId3-deficient mice immunized with a T-cell-dependent antigen and a type 2 T-cell-independent antigen are attenuated and severely impaired, respectively. Further analysis of lymphocytes isolated from Id3-deficient mice reveals a B-cell defect in their proliferation response to BCR cross-linking but not to lipopolysaccharide or a combination of BCR cross-linking and interleukin-4. Analyses of cultured lymphocytes also suggest involvement of Id3 in cytokine production in T cells and isotype switching in B cells. Finally, the proliferation defect inId3-deficient B cells can be rescued by ectopic expression of Id1, a homologue of Id3. Taken together, these results define a necessary and specific role for Id3 in mediating signals from BCR to cell cycle progression during humoral immune responses.

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