scholarly journals B Cells Are Essential for Moderating the Inflammatory Response and Controlling Bacterial Multiplication in a Mouse Model of Vaccination against Chlamydophila abortus Infection

2009 ◽  
Vol 77 (11) ◽  
pp. 4868-4876 ◽  
Author(s):  
Antonio J. Buendía ◽  
Nieves Ortega ◽  
María R. Caro ◽  
Laura Del Río ◽  
María C. Gallego ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Inflammatory Response ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Immune Serum ◽  
Chlamydophila Abortus ◽  
Cytokines And Chemokines ◽  
Deficient Mice

ABSTRACT The use of inactivated vaccines associated with suitable adjuvants has been demonstrated to confer a good level of protection against Chlamydophila abortus. However, the basis of the immune protective response induced by these vaccines has been poorly studied. B cells act as an immune regulatory population during primary infection by C. abortus. Thus, it was considered of interest to study the role of B cells in an infection after immunization with a killed vaccine. For this, C57BL/6 and B-cell-deficient mice were immunized with a killed vaccine against C. abortus using QS-21 as the adjuvant. After challenge, the course of infection was established by analysis of morbidity, C. abortus burden in the liver, and histopathological changes. The immune response induced was studied by real-time PCR techniques. Experiments involving transfer of immune serum from vaccinated or previously infected mice were also carried out. The lack of B cells reduced the protection conferred by the QS-21 adjuvant vaccine. Vaccinated B-cell-deficient mice showed a 1,000-fold-greater bacterial burden in the liver than their wild-type counterparts. Obvious differences existed in the liver, where a severe neutrophilic reaction and extended areas of necrosis were observed with vaccinated B-cell-deficient mice. An analysis of the immune response pointed to a significant increase in inflammatory cytokines and chemokines and the deficient production of transforming growth factor beta. The transfer of antibodies restored the level of protection. This study demonstrates that B cells play a crucial role in controlling C. abortus multiplication and prevent an exacerbated inflammatory response.

scholarly journals B-Cell-Deficient Mice Show an Exacerbated Inflammatory Response in a Model of Chlamydophila abortus Infection

2002 ◽  
Vol 70 (12) ◽  
pp. 6911-6918 ◽  
Author(s):  
Antonio J. Buendía ◽  
Laura Del Río ◽  
Nieves Ortega ◽  
Joaquín Sánchez ◽  
María C. Gallego ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Immunoglobulin M ◽  
Chlamydia Psittaci ◽  
Chlamydophila Abortus ◽  
Serotype 1

ABSTRACT The resolution of Chlamydophila abortus (Chlamydia psittaci serotype 1) infection is dependent on gamma interferon and CD8+ T cells, and classically, B cells have been considered to play a minimal role in host defense. The role of B cells in the immune response was studied by using a model of infection in mice with genetically modified immunoglobulin M transmembrane domains (μMT). In the absence of B cells, infection with C. abortus leads to an acute severe fatal disease that involves a disseminated intravascular coagulation syndrome. μMT mice displayed an increased level of proinflammatory cytokines in serum, and an increased number of neutrophils was observed in the lesions. The possible deleterious role of neutrophils in the pathogenesis of disease in μMT mice was determined by depletion of the neutrophils with the monoclonal antibody RB6-8C5. This led to an enhancement of the bacterial burden and early mortality in both μMT and wild-type mice, while necrotic lesions remained. Analysis of the presence of immunoregulatory cytokines showed significantly lower levels of transforming growth factor β in the sera of μMT mice. However, mice lacking mature B cells were able to establish a specific immune response that protected them from a secondary challenge. Taken together, these data suggest an immunomodulatory role for B cells in the early events of C. abortus primary infection that can protect mice against an exaggerated inflammatory response.

scholarly journals B Cells Are Essential for Vaccination-Induced Resistance to Virulent Toxoplasma gondii

2000 ◽  
Vol 68 (3) ◽  
pp. 1026-1033 ◽  
Author(s):  
Peter C. Sayles ◽  
George W. Gibson ◽  
Lawrence L. Johnson
Keyword(s):  
B Cells ◽  
Toxoplasma Gondii ◽  
B Cell ◽  
Induced Resistance ◽  
Immune Serum ◽  
Challenge Infection ◽  
Host Cells ◽  
Cell Functions ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT T lymphocytes and gamma interferon (IFN-γ) are known mediators of immune resistance to Toxoplasma gondii infection, but whether B cells also play an important role is not clear. We have investigated this issue using B-cell-deficient (μMT) mice. If vaccinated with attenuated T. gondii tachyzoites, μMT mice are susceptible to a challenge intraperitoneal infection with highly virulent tachyzoites that similarly vaccinated B-cell-sufficient mice resist. Susceptibility is evidenced by increased numbers of parasites at the challenge infection site and by extensive mortality. The susceptibility of B-cell-deficient mice does not appear to be caused by deficient T-cell functions or diminished capacity of vaccinated and challenged B-cell-deficient mice to produce IFN-γ. Administration of Toxoplasma-immune serum, but not nonimmune serum, to vaccinated B-cell-deficient mice significantly prolongs their survival after challenge with virulent tachyzoites. Vaccinated mice lacking Fc receptors or the fifth component of complement resist a challenge infection, suggesting that neither Fc-receptor-dependent phagocytosis of antibody-coated tachyzoites nor antibody-dependent cellular cytotoxicity nor antibody-and-complement-dependent lysis of tachyzoites is a crucial mechanism of resistance. However, Toxoplasma-immune serum effectively inhibits the infection of host cells by tachyzoites in vitro. Together, the results support the hypothesis that B cells are required for vaccination-induced resistance to virulent tachyzoites in order to produce antibodies and that antibodies may function protectively in vivo by blocking infection of host cells by tachyzoites.

scholarly journals Beta transforming growth factors are potential regulators of B lymphopoiesis.

1987 ◽  
Vol 166 (5) ◽  
pp. 1290-1299 ◽  
Author(s):  
G Lee ◽  
L R Ellingsworth ◽  
S Gillis ◽  
R Wall ◽  
P W Kincade
Keyword(s):  
B Cells ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Negative Regulator ◽  
B Cell Differentiation ◽  
B Lymphopoiesis ◽  
Tgf Beta ◽  
Ifn Gamma ◽  
Serum Factors

Members of the transforming growth factor beta (TGF-beta) family of polypeptides were found to be potent in vitro inhibitors of kappa light chain expression on normal bone marrow-derived and transformed cloned pre-B cells, and of the maturation of these cells to mitogen responsiveness. The inhibition by TGF-beta was selective in that Ia expression was not blocked. Together with the observations that LPS, IL-1, NZB serum factors, IL-4, and IFN-gamma preferentially induced either kappa or Ia, or both, on a pre-B cell line, these results further suggest that acquisition of Ig and class II molecules is independently controlled by different antagonists as well as agonists. In addition, kappa chain induction by IFN-gamma does not appear to be as sensitive to TGF-beta downregulation as that stimulated by other factors tested, and this raises the possibility that activation of the same gene may result from different transmembrane signaling pathways. In contrast to the inhibitory effects of TGF-beta on kappa acquisition by pre-B cells and on kappa increase after exposure of mature B cells to LPS, as measured by kappa RNA levels and/or surface fluorescence, no inhibition was observed on unstimulated spleen B cells or on two cloned B cell lines that constitutively produce kappa. Thus, TGF-beta may function during specific stages of B cell differentiation by inhibiting initiation of, or increased transcription of Ig genes, and therefore, may be an important negative regulator of B lymphopoiesis. It is the first natural substance found to have this effect.

Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1144-1152 ◽  
Author(s):  
Lisa Westerberg ◽  
Malin Larsson ◽  
Samantha J. Hardy ◽  
Carmen Fernández ◽  
Adrian J. Thrasher ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Humoral Immune Response ◽  
Wiskott Aldrich Syndrome ◽  
Humoral Immune ◽  
Germinal Center Reaction ◽  
Syndrome Protein ◽  
Deficient Mice

Abstract The Wiskott-Aldrich syndrome protein (WASp) is mutated in the severe immunodeficiency disease Wiskott-Aldrich syndrome (WAS). The function of B cells and the physiologic alterations in WAS remain unclear. We show that B cells from WAS patients exhibited decreased motility and had reduced capacity to migrate, adhere homotypically, and form long protrusions after in vitro culture. WASp-deficient murine B cells also migrated less well to chemokines. Upon antigen challenge, WASp-deficient mice mounted a reduced and delayed humoral immune response to both T-cell–dependent and –independent antigens. This was at least in part due to deficient migration and homing of B cells. In addition, the germinal center reaction was reduced in WASp-deficient mice. Thus, WASp is crucial for optimal B-cell responses and plays a pivotal role in the primary humoral immune response.

scholarly journals Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3173-3181
Author(s):  
AC Fluckiger ◽  
JF Rossi ◽  
A Bussel ◽  
P Bryon ◽  
J Banchereau ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lymphocytic Leukemia ◽  
Interleukin 4 ◽  
Aureus Strain ◽  
Cross Linking ◽  
Cell Recovery

Recent studies performed in the laboratory have established that interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody (MoAb) 89 presented on Ltk- mouse fibroblasts stably expressing human Fc gamma RII/CDw32 (referred to as the CD40 system) sustains long-term proliferation of normal human B cells. In the present study, B-cell chronic lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined for their capacity to proliferate and differentiate in response to various cytokines. Our results indicate that the outcome of IL-4 stimulation on the in vitro growth of B-CLL depends on the signalling pathway used for their activation. Whereas IL-4 did not display any growth-stimulatory effect on B-CLL activated by Ig cross-linking agents, it could stimulate DNA synthesis and enhance the viable cell recovery when leukemic B cells were cultured in the CD40 system. Most B-CLL samples were induced for IgM synthesis upon Staphylococcus aureus strain Cowan I stimulation. This Ig response was potentiated by IL-2 and antagonized by IL-4. Anti-CD40 MoAb used alone or in combination with cytokines (IL-1 alpha to IL-6, interferon gamma, tumor necrosis factor gamma, and transforming growth factor beta) failed to induce Ig secretion from B-CLL cells. No evidence for Ig isotype switching was obtained with the cytokines listed above, regardless of the mode of activation. Taken together, our results suggest that B-CLL cells can be partially released from their apparent maturation block by IL-2 and Ig cross-linking agents. In contrast, combinations of IL-4 and cross-linked anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly stimulated their differentiation into Ig secreting cells.

scholarly journals A follicular regulatory Innate Lymphoid Cell population impairs interactions between germinal center Tfh and B cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Margaret H. O’Connor ◽  
Roshell Muir ◽  
Marita Chakhtoura ◽  
Michael Fang ◽  
Eirini Moysi ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Germinal Center ◽  
Transforming Growth Factor ◽  
Cell Interactions ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Follicular Helper ◽  
Lymphoid Cell Population

AbstractInnate Lymphoid Cells (ILCs) are immune cells typically found on mucosal surfaces and in secondary lymphoid organs where they regulate the immune response to pathogens. Despite their key role in the immune response, there are still fundamental gaps in our understanding of ILCs. Here we report a human ILC population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILCFR) that to our knowledge has not been previously identified. ILCFR have a distinct phenotype and transcriptional program when compared to other defined ILCs. Surprisingly, ILCFR inhibit the ability of follicular helper T (Tfh) cells to provide B cell help. The localization of ILCFR to the germinal centers suggests these cells may interfere with germinal center B cell (GC-B) and germinal center Tfh cell (GC-Tfh) interactions through the production of transforming growth factor beta (TGF-β. Intriguingly, under conditions of impaired GC-Tfh-GC-B cell interactions, such as human immunodeficiency virus (HIV) infection, the frequency of these cells is increased. Overall, we predict a role for ILCFR in regulating GC-Tfh-GC-B cell interactions and propose they expand in chronic inflammatory conditions.

scholarly journals Effect of downregulation of germline transcripts on immunoglobulin A isotype differentiation.

1993 ◽  
Vol 178 (1) ◽  
pp. 129-138 ◽  
Author(s):  
Y Wakatsuki ◽  
W Strober
Keyword(s):  
B Cells ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Immunoglobulin A ◽  
State Level ◽  
Interleukin 4 ◽  
Tgf Beta ◽  
Switch Differentiation

In this study we determined the role of immunoglobulin (Ig) germline transcripts in the isotype switch differentiation of the cloned lymphoma B cell line CH12.LX. In initial studies, we showed that addition of transforming growth factor beta (TGF-beta) and interleukin 4 (IL-4), either alone or in combination, augment switching from membrane (m)IgM+ to mIgA+ cells, and that increased switching is preceded and paralleled by an increase in the steady-state level of alpha germline transcripts (alpha GLT). Interestingly, TGF-beta and IL-4 affect switching in different ways, as shown by the fact that IL-4 increases and TGF-beta decreases the number of dual-positive (mIgM+/mIgA+) cells; in addition, TGF-beta and IL-4 have different effects on the time course of induction of alpha GLT. In subsequent studies, we established that we could downregulate alpha GLT levels in CH12.LX B cells by transfecting an expression vector that can be induced to produce transcripts antisense to the I alpha exon. Using this approach we downregulated alpha GLT in CH12.LX B cells undergoing switching in the presence of TGF-beta and IL-4 and showed that such downregulation led to decreased switching, as evidenced by decreased appearance of dual-positive B cells as well as decreased IgA synthesis relative to IgM synthesis. This result was corroborated by the fact that incubation of CH12.LX cells with phosphorothio-oligo antisense DNA to I alpha sequence also led to a decrease in the number of dual-positive cells and in the IgA/IgM secretion ratio. In summary, IgA isotype differentiation in CH12.LX B cell, particularly the steps necessary for the elaboration of mIgM+/mIgA+ switch intermediate cells, is inhibited by downregulation of alpha GLT; it is therefore apparent that alpha GLT plays a key role in the initial stage of isotype switch differentiation.

scholarly journals Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors

Blood ◽  
1992 ◽  
Vol 80 (12) ◽  
pp. 3173-3181 ◽  
Author(s):  
AC Fluckiger ◽  
JF Rossi ◽  
A Bussel ◽  
P Bryon ◽  
J Banchereau ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lymphocytic Leukemia ◽  
Interleukin 4 ◽  
Aureus Strain ◽  
Cross Linking ◽  
Cell Recovery

Abstract Recent studies performed in the laboratory have established that interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody (MoAb) 89 presented on Ltk- mouse fibroblasts stably expressing human Fc gamma RII/CDw32 (referred to as the CD40 system) sustains long-term proliferation of normal human B cells. In the present study, B-cell chronic lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined for their capacity to proliferate and differentiate in response to various cytokines. Our results indicate that the outcome of IL-4 stimulation on the in vitro growth of B-CLL depends on the signalling pathway used for their activation. Whereas IL-4 did not display any growth-stimulatory effect on B-CLL activated by Ig cross-linking agents, it could stimulate DNA synthesis and enhance the viable cell recovery when leukemic B cells were cultured in the CD40 system. Most B-CLL samples were induced for IgM synthesis upon Staphylococcus aureus strain Cowan I stimulation. This Ig response was potentiated by IL-2 and antagonized by IL-4. Anti-CD40 MoAb used alone or in combination with cytokines (IL-1 alpha to IL-6, interferon gamma, tumor necrosis factor gamma, and transforming growth factor beta) failed to induce Ig secretion from B-CLL cells. No evidence for Ig isotype switching was obtained with the cytokines listed above, regardless of the mode of activation. Taken together, our results suggest that B-CLL cells can be partially released from their apparent maturation block by IL-2 and Ig cross-linking agents. In contrast, combinations of IL-4 and cross-linked anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly stimulated their differentiation into Ig secreting cells.

scholarly journals Cytokine mRNA expression during an in vitro response of human B lymphocytes: kinetics of B cell tumor necrosis factor alpha, interleukin (IL)6, IL-10, and transforming growth factor beta 1 mRNAs.

1993 ◽  
Vol 178 (2) ◽  
pp. 521-528 ◽  
Author(s):  
T Matthes ◽  
C Werner-Favre ◽  
H Tang ◽  
X Zhang ◽  
V Kindler ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Necrosis Factor Alpha ◽  
Cell Clones ◽  
In Vitro Response ◽  
Factor Alpha ◽  
Necrosis Factor

Expression of mRNA for eight cytokines was analyzed in an in vitro response-proliferation and Ig-secretion--of normal human B lymphocytes. This was made possible by the use of murine thymoma cells as helper cells in conjunction with human T cell supernatant, and the design of human DNA sequence-specific primers for RT-polymerase chain reaction. mRNAs for interleukin (IL)2 and IL-4, but also for IL-1 alpha and IL-1 beta remained undetectable during the whole culture period in highly purified B cells prepared by a three-step purification protocol. However, tumor necrosis factor alpha and IL-6 mRNAs peaked during days 1-3 after culture start and became undetectable after 5-6 d, shortly before bulk B cell proliferation started to decline. In contrast, transforming growth factor beta 1 mRNA, after a progressive increase during the first few days, and IL-10 mRNA, after a peak on days 1-3, remained detectable in immunoglobulin (Ig)-secreting cultures throughout the observation period of 22 d. Clonal analysis on 8-d cultures that had been seeded with single B cells by autocloning with the cell sorter, revealed that 85% of 77 B cell clones studied, expressed TGF-beta 1 mRNA, and only 19% IL-10 mRNA. These findings show a differentiation stage-related cytokine program during a B cell response, whereby (a) B cells can become activated without IL-1 alpha or IL-1 beta expression; (b) mRNA for positive (IL-10) and negative (TGF-beta 1) autoregulatory factors coexists in cell populations during the later phase of the response, although not necessarily in all B cell clones; and (c) normal Ig-secreting cells cease IL-6 expression in contrast to their malignant counterparts, myeloma cells.

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