scholarly journals Specific Humoral Immunity versus Polyclonal B Cell Activation in Trypanosoma cruzi Infection of Susceptible and Resistant Mice

2010 ◽  
Vol 4 (7) ◽  
pp. e733 ◽  
Author(s):  
Marianne A. Bryan ◽  
Siobhan E. Guyach ◽  
Karen A. Norris
Keyword(s):  
Trypanosoma Cruzi ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cruzi Infection

scholarly journals PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice

2017 ◽  
Vol 114 (44) ◽  
pp. E9328-E9337 ◽  
Author(s):  
Dan Su ◽  
Stijn Vanhee ◽  
Rebeca Soria ◽  
Elin Jaensson Gyllenbäck ◽  
Linda M. Starnes ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Transactivation Domain ◽  
B Cell Activation ◽  
Chromatin Regulator ◽  
B Cell Subsets

B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts at several junctures of B lineage maturation and effector cell differentiation by controlling B cell activation.

scholarly journals LT-K63 Enhances B Cell Activation and Survival Factors in Neonatal Mice That Translates Into Long-Lived Humoral Immunity

2020 ◽  
Vol 11 ◽  
Author(s):  
Audur Anna Aradottir Pind ◽  
Jenny Lorena Molina Estupiñan ◽  
Gudbjorg Julia Magnusdottir ◽  
Giuseppe Del Giudice ◽  
Ingileif Jonsdottir ◽  
...  
Keyword(s):  
B Cell ◽  
Humoral Immunity ◽  
Cell Activation ◽  
B Cell Activation ◽  
Survival Factors ◽  
Neonatal Mice

scholarly journals Genetic Immunization Converts the Trypanosoma cruzi B-Cell Mitogen Proline Racemase to an Effective Immunogen

2009 ◽  
Vol 78 (2) ◽  
pp. 810-822 ◽  
Author(s):  
Marianne A. Bryan ◽  
Karen A. Norris
Keyword(s):  
B Cells ◽  
Trypanosoma Cruzi ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Genetic Immunization ◽  
Murine Splenocytes ◽  
Specific Igg ◽  
Cell Mitogen ◽  
Antibody Secretion

ABSTRACT Trypanosoma cruzi is the etiologic agent of Chagas' disease. Acute T. cruzi infection results in polyclonal B-cell activation and delayed specific humoral immunity. T. cruzi proline racemase (TcPRAC), a T. cruzi B-cell mitogen, may contribute to this dysfunctional humoral response. Stimulation of murine splenocytes with recombinant protein (rTcPRAC) induced B-cell proliferation, antibody secretion, interleukin-10 (IL-10) production, and upregulation of CD69 and CD86 on B cells. Marginal zone (MZ) B cells are more responsive to T-cell-independent (TI) rTcPRAC stimulation than are follicular mature (FM) B cells in terms of proliferation, antibody secretion, and IL-10 production. During experimental T. cruzi infection, TcPRAC-specific IgG remained undetectable when responses to other T. cruzi antigens developed. Conversely, intradermal genetic immunization via gene gun (GG) delivered TcPRAC as an immunogen, generating high-titer TcPRAC-specific IgG without B-cell dysfunction. TcPRAC GG immunization led to antigen-specific splenic memory B-cell and bone marrow plasma cell formation. TcPRAC-specific IgG bound mitogenic rTcPRAC, decreasing subsequent B-cell activation. GG immunization with rTcPRAC DNA was nonmitogenic and did not affect the generation of specific IgG to another T. cruzi antigen, complement regulatory protein (CRP). These data demonstrate the utility of genetic immunization for the conversion of a protein mitogen to an effective antigen. Furthermore, coimmunization of TcPRAC with another T. cruzi antigen indicates the usefulness of this approach for multivalent vaccine development.

scholarly journals Genetic mapping reveals Nfkbid as a central regulator of humoral immunity to Toxoplasma gondii

2021 ◽  
Vol 17 (12) ◽  
pp. e1010081
Author(s):  
Scott P. Souza ◽  
Samantha D. Splitt ◽  
Juan C. Sanchez-Arcila ◽  
Julia A. Alvarez ◽  
Jessica N. Wilson ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Activation ◽  
Secondary Infection ◽  
Forward Genetics ◽  
Parasitic Infections ◽  
B Cell Activation ◽  
Class Switch ◽  
Secondary Infections

Protective immunity to parasitic infections has been difficult to elicit by vaccines. Among parasites that evade vaccine-induced immunity is Toxoplasma gondii, which causes lethal secondary infections in chronically infected mice. Here we report that unlike susceptible C57BL/6J mice, A/J mice were highly resistant to secondary infection. To identify correlates of immunity, we utilized forward genetics to identify Nfkbid, a nuclear regulator of NF-κB that is required for B cell activation and B-1 cell development. Nfkbid-null mice (“bumble”) did not generate parasite-specific IgM and lacked robust parasite-specific IgG, which correlated with defects in B-2 cell maturation and class-switch recombination. Though high-affinity antibodies were B-2 derived, transfer of B-1 cells partially rescued the immunity defects observed in bumble mice and were required for 100% vaccine efficacy in bone marrow chimeric mice. Immunity in resistant mice correlated with robust isotype class-switching in both B cell lineages, which can be fine-tuned by Nfkbid gene expression. We propose a model whereby humoral immunity to T. gondii is regulated by Nfkbid and requires B-1 and B-2 cells for full protection.

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