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Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax®23.

Roth A, Glaesener S, Schütz K, Meyer-Bahlburg A - PLoS ONE (2016)

Bottom Line: We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations.Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23.Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.

ABSTRACT
Protective immunity against T cell independent (TI) antigens such as Streptococcus pneumoniae is characterized by antibody production of B cells induced by the combined activation of T cell independent type 1 and type 2 antigens in the absence of direct T cell help. In mice, the main players in TI immune responses have been well defined as marginal zone (MZ) B cells and B-1 cells. However, the existence of human equivalents to these B cell subsets and the nature of the human B cell compartment involved in the immune reaction remain elusive. We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations. Our data demonstrates a transient decrease of transitional and naïve B cells, with a concomitant increase of IgA+ but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific IgA+ producing plasma cells. No alterations could be detected in T cells, or proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI immune response, antigen-specific memory responses could not be observed. Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23. Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment. Those modulations occur in the absence of any modulations of T cells and without the development of a specific memory response.

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Related in: MedlinePlus

Vaccination with Pneumovax®23 does not generate a detectable memory response after 90 days.(A) Number of PnPS-specific antibody producing cells within CD27+ memory, and CD27- naïve mature B cells purified by cell sorting 90 days after vaccination with Pneumovax®23. (B) Cord blood cells (CB), and PBMC of healthy adults not recently vaccinated with Pneumovax®23 (AB) were stimulated with a combination of IL-4/IL-21/anti-CD40/CpG/BAFF for 5 days, then examined for their PnPS-specific Ig production by ELISPOT. (*p<0.05, **p<0.01)
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pone.0152215.g005: Vaccination with Pneumovax®23 does not generate a detectable memory response after 90 days.(A) Number of PnPS-specific antibody producing cells within CD27+ memory, and CD27- naïve mature B cells purified by cell sorting 90 days after vaccination with Pneumovax®23. (B) Cord blood cells (CB), and PBMC of healthy adults not recently vaccinated with Pneumovax®23 (AB) were stimulated with a combination of IL-4/IL-21/anti-CD40/CpG/BAFF for 5 days, then examined for their PnPS-specific Ig production by ELISPOT. (*p<0.05, **p<0.01)

Mentions: In order to determine the maintenance of immunological memory, we examined peripheral memory B cells by ELISpot assays for their capacity to produce PnPS-specific immunoglobulins three months after Pneumovax®23 immunization. Sort-purified CD27+ memory, and CD27- B cells were stimulated with the TLR7/TLR8 agonist R848 combined with IL2 for 5 and 8 days [33]. Day 5 was found to be optimal for the detection of ASC, which were predominantly of the IgM-isotype (CD27+ p = 0.002; CD27- p = 0.048) without significant difference between CD27+ and CD27- B cells. Few antigen-specific IgG ASC could also be detected (Fig 5A). As a positive control, we determined tetanus toxoid in individuals that had received immunization with tetanus toxoid vaccine within the last 10 years. As expected, stimulation of PBMC resulted in the generation of tetanus toxoid-specific IgG ASC, but not IgA or IgM (data not shown).


Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax®23.

Roth A, Glaesener S, Schütz K, Meyer-Bahlburg A - PLoS ONE (2016)

Vaccination with Pneumovax®23 does not generate a detectable memory response after 90 days.(A) Number of PnPS-specific antibody producing cells within CD27+ memory, and CD27- naïve mature B cells purified by cell sorting 90 days after vaccination with Pneumovax®23. (B) Cord blood cells (CB), and PBMC of healthy adults not recently vaccinated with Pneumovax®23 (AB) were stimulated with a combination of IL-4/IL-21/anti-CD40/CpG/BAFF for 5 days, then examined for their PnPS-specific Ig production by ELISPOT. (*p<0.05, **p<0.01)
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4816312&req=5

pone.0152215.g005: Vaccination with Pneumovax®23 does not generate a detectable memory response after 90 days.(A) Number of PnPS-specific antibody producing cells within CD27+ memory, and CD27- naïve mature B cells purified by cell sorting 90 days after vaccination with Pneumovax®23. (B) Cord blood cells (CB), and PBMC of healthy adults not recently vaccinated with Pneumovax®23 (AB) were stimulated with a combination of IL-4/IL-21/anti-CD40/CpG/BAFF for 5 days, then examined for their PnPS-specific Ig production by ELISPOT. (*p<0.05, **p<0.01)
Mentions: In order to determine the maintenance of immunological memory, we examined peripheral memory B cells by ELISpot assays for their capacity to produce PnPS-specific immunoglobulins three months after Pneumovax®23 immunization. Sort-purified CD27+ memory, and CD27- B cells were stimulated with the TLR7/TLR8 agonist R848 combined with IL2 for 5 and 8 days [33]. Day 5 was found to be optimal for the detection of ASC, which were predominantly of the IgM-isotype (CD27+ p = 0.002; CD27- p = 0.048) without significant difference between CD27+ and CD27- B cells. Few antigen-specific IgG ASC could also be detected (Fig 5A). As a positive control, we determined tetanus toxoid in individuals that had received immunization with tetanus toxoid vaccine within the last 10 years. As expected, stimulation of PBMC resulted in the generation of tetanus toxoid-specific IgG ASC, but not IgA or IgM (data not shown).

Bottom Line: We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations.Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23.Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.

ABSTRACT
Protective immunity against T cell independent (TI) antigens such as Streptococcus pneumoniae is characterized by antibody production of B cells induced by the combined activation of T cell independent type 1 and type 2 antigens in the absence of direct T cell help. In mice, the main players in TI immune responses have been well defined as marginal zone (MZ) B cells and B-1 cells. However, the existence of human equivalents to these B cell subsets and the nature of the human B cell compartment involved in the immune reaction remain elusive. We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations. Our data demonstrates a transient decrease of transitional and naïve B cells, with a concomitant increase of IgA+ but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific IgA+ producing plasma cells. No alterations could be detected in T cells, or proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI immune response, antigen-specific memory responses could not be observed. Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23. Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment. Those modulations occur in the absence of any modulations of T cells and without the development of a specific memory response.

Show MeSH
Related in: MedlinePlus