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Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool

View Article: PubMed Central - PubMed

ABSTRACT

We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM-IgG+ cells responded by the production of antigen-specific IgG while the IgM+ memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers. The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond. Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets. We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells. By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy.

No MeSH data available.


Related in: MedlinePlus

Regulation of the size of the memory B cell pool.Rag2-/- recipient mice were injected with different numbers of naive SWHEL.AID/YFP.Rag2-/- B cells and OTII.Rag2-/- naive CD4 T cells and immunized as in Fig 1. The correlations between the number of injected B cells and (A) the number of total splenic B cells recovered, (B) the number of splenic AID/YFP+ memory B cells recovered 8 weeks after immunization and (C) the level of anti-HEL specific IgG in the serum are shown. For each plot, linear regression coefficient R2 is shown.
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pone.0167003.g004: Regulation of the size of the memory B cell pool.Rag2-/- recipient mice were injected with different numbers of naive SWHEL.AID/YFP.Rag2-/- B cells and OTII.Rag2-/- naive CD4 T cells and immunized as in Fig 1. The correlations between the number of injected B cells and (A) the number of total splenic B cells recovered, (B) the number of splenic AID/YFP+ memory B cells recovered 8 weeks after immunization and (C) the level of anti-HEL specific IgG in the serum are shown. For each plot, linear regression coefficient R2 is shown.

Mentions: It is not yet known whether the number of antigen-experienced memory B cells correlated to the number of naïve B cells or if it is controlled independently of the initial number of antigen-specific B cells present. To approach this question we transferred different numbers of mature naïve B cells from SWHEL.AID/YFP.Rag2-/- donors (ranging from 105 to 5.106) into Rag2-deficient mice together with an excess of CD4+ T helper cells (106) and immunize the hosts the day after cell transfer with OVA-HEL in optimal non-limiting quantities. To directly compare the results obtained after the transfer of different all numbers we allowed the responses to reach steady-state eight weeks after antigenic challenge. We studied the amplitude of the immune response by measuring the serum titers of HEL-specific IgG antibodies and enumerating the number of HEL-specific B cells recovered. We found that in the presence of excess T cell help, the levels of the HEL-specific IgGs (Fig 4C), and both the total number of HEL-specific (Fig 4A) and of memory YFP+ B cells recovered (Fig 4B), did not correlate to the number of antigen specific naïve B cells initially transferred.


Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool
Regulation of the size of the memory B cell pool.Rag2-/- recipient mice were injected with different numbers of naive SWHEL.AID/YFP.Rag2-/- B cells and OTII.Rag2-/- naive CD4 T cells and immunized as in Fig 1. The correlations between the number of injected B cells and (A) the number of total splenic B cells recovered, (B) the number of splenic AID/YFP+ memory B cells recovered 8 weeks after immunization and (C) the level of anti-HEL specific IgG in the serum are shown. For each plot, linear regression coefficient R2 is shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120830&req=5

pone.0167003.g004: Regulation of the size of the memory B cell pool.Rag2-/- recipient mice were injected with different numbers of naive SWHEL.AID/YFP.Rag2-/- B cells and OTII.Rag2-/- naive CD4 T cells and immunized as in Fig 1. The correlations between the number of injected B cells and (A) the number of total splenic B cells recovered, (B) the number of splenic AID/YFP+ memory B cells recovered 8 weeks after immunization and (C) the level of anti-HEL specific IgG in the serum are shown. For each plot, linear regression coefficient R2 is shown.
Mentions: It is not yet known whether the number of antigen-experienced memory B cells correlated to the number of naïve B cells or if it is controlled independently of the initial number of antigen-specific B cells present. To approach this question we transferred different numbers of mature naïve B cells from SWHEL.AID/YFP.Rag2-/- donors (ranging from 105 to 5.106) into Rag2-deficient mice together with an excess of CD4+ T helper cells (106) and immunize the hosts the day after cell transfer with OVA-HEL in optimal non-limiting quantities. To directly compare the results obtained after the transfer of different all numbers we allowed the responses to reach steady-state eight weeks after antigenic challenge. We studied the amplitude of the immune response by measuring the serum titers of HEL-specific IgG antibodies and enumerating the number of HEL-specific B cells recovered. We found that in the presence of excess T cell help, the levels of the HEL-specific IgGs (Fig 4C), and both the total number of HEL-specific (Fig 4A) and of memory YFP+ B cells recovered (Fig 4B), did not correlate to the number of antigen specific naïve B cells initially transferred.

View Article: PubMed Central - PubMed

ABSTRACT

We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM-IgG+ cells responded by the production of antigen-specific IgG while the IgM+ memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers. The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond. Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets. We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells. By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy.

No MeSH data available.


Related in: MedlinePlus