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Activation of virus-specific memory B cells in the absence of T cell help.

Hebeis BJ, Klenovsek K, Rohwer P, Ritter U, Schneider A, Mach M, Winkler TH - J. Exp. Med. (2004)

Bottom Line: Antigenic stimulation 4-6 d after transfer of B cells resulted in rapid IgG production.Transfer of memory B cells into immunocompetent animals indicated that presence of helper T cells did not enhance the memory B cell response.Therefore, our results indicate that activation of virus-specific memory B cells to secrete IgG is independent of cognate or bystander T cell help.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.

ABSTRACT
Humoral immunity is maintained by long-lived plasma cells, constitutively secreting antibodies, and nonsecreting resting memory B cells that are rapidly reactivated upon antigen encounter. The activation requirements for resting memory B cells, particularly the role of T helper cells, are unclear. To analyze the activation of memory B cells, mice were immunized with human cytomegalovirus, a complex human herpesvirus, and tick-born encephalitis virus, and a simple flavivirus. B cell populations devoid of Ig-secreting plasma cells were adoptively transferred into T and B cell-deficient RAG-1-/- mice. Antigenic stimulation 4-6 d after transfer of B cells resulted in rapid IgG production. The response was long lasting and strictly antigen specific, excluding polyclonal B cell activation. CD4+ T cells were not involved since (a) further depletion of CD4+ T cells in the recipient mice did not alter the antibody response and (b) recipient mice contained no detectable CD4+ T cells 90 d posttransfer. Memory B cells could not be activated by a soluble viral protein without T cell help. Transfer of memory B cells into immunocompetent animals indicated that presence of helper T cells did not enhance the memory B cell response. Therefore, our results indicate that activation of virus-specific memory B cells to secrete IgG is independent of cognate or bystander T cell help.

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IgG memory response in recipient mice with altered lymphoid architecture. 5 × 106 sorted B cells from a pool of hyperimmunized C57BL/6 mice were transferred as described in the legend for Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. Control C57BL/6 mice were treated with GK1.5 antibody but received no memory B cell preparations. The IgG antibody response in different recipient mice treated with GK1.5 antibody was measured 7 d after challenge with 2 μg HCMV-DBs i.v. The bars represent the mean of RI values; dots are individual values. The experiment was repeated, and similar results were obtained.
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fig7: IgG memory response in recipient mice with altered lymphoid architecture. 5 × 106 sorted B cells from a pool of hyperimmunized C57BL/6 mice were transferred as described in the legend for Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. Control C57BL/6 mice were treated with GK1.5 antibody but received no memory B cell preparations. The IgG antibody response in different recipient mice treated with GK1.5 antibody was measured 7 d after challenge with 2 μg HCMV-DBs i.v. The bars represent the mean of RI values; dots are individual values. The experiment was repeated, and similar results were obtained.

Mentions: In a series of experiments, we noted that transferred memory B cells were unresponsive to challenge with HCMV-DBs when the antigen was applied within minutes after the injection of memory B cell preparations, a protocol that is widely used for the assessment of memory B cell function. This effect was observed in RAG-1−/− recipients, T cell−/− mice, and anti-CD4–treated recipients. In contrast, when virus particles were given 24 h after adoptive transfer, a full response was measurable in T cell−/− mice (unpublished data). These findings suggested that memory B cells needed to migrate to a specific lymphoid compartment in order to become fully responsive to antigenic stimulation in a T cell–independent way. To test this, we used TNF−/− and TNF/LTα−/− mice as recipients in which the organization of the lymphoid architecture is severely altered (20). Wild-type, TNF−/−, and TNF/LTα−/− C57BL/6 mice were treated with anti-CD4–specific antibody, and memory B cell preparations were adoptively transferred. An IgG memory response was clearly detectable in anti-CD4–treated wild-type mice, whereas only a minute IgG response was detected in TNF−/− recipients (Fig. 7). In TNF/LTα−/− recipients, the IgG memory response was completely absent, likewise in anti-CD4–treated C57BL/6 mice that had not received memory cells (Fig. 7). These results indicate that homing of memory B cells to secondary lymphoid tissue is required for the T cell–independent memory B cell response.


Activation of virus-specific memory B cells in the absence of T cell help.

Hebeis BJ, Klenovsek K, Rohwer P, Ritter U, Schneider A, Mach M, Winkler TH - J. Exp. Med. (2004)

IgG memory response in recipient mice with altered lymphoid architecture. 5 × 106 sorted B cells from a pool of hyperimmunized C57BL/6 mice were transferred as described in the legend for Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. Control C57BL/6 mice were treated with GK1.5 antibody but received no memory B cell preparations. The IgG antibody response in different recipient mice treated with GK1.5 antibody was measured 7 d after challenge with 2 μg HCMV-DBs i.v. The bars represent the mean of RI values; dots are individual values. The experiment was repeated, and similar results were obtained.
© Copyright Policy
Related In: Results  -  Collection

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fig7: IgG memory response in recipient mice with altered lymphoid architecture. 5 × 106 sorted B cells from a pool of hyperimmunized C57BL/6 mice were transferred as described in the legend for Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. Control C57BL/6 mice were treated with GK1.5 antibody but received no memory B cell preparations. The IgG antibody response in different recipient mice treated with GK1.5 antibody was measured 7 d after challenge with 2 μg HCMV-DBs i.v. The bars represent the mean of RI values; dots are individual values. The experiment was repeated, and similar results were obtained.
Mentions: In a series of experiments, we noted that transferred memory B cells were unresponsive to challenge with HCMV-DBs when the antigen was applied within minutes after the injection of memory B cell preparations, a protocol that is widely used for the assessment of memory B cell function. This effect was observed in RAG-1−/− recipients, T cell−/− mice, and anti-CD4–treated recipients. In contrast, when virus particles were given 24 h after adoptive transfer, a full response was measurable in T cell−/− mice (unpublished data). These findings suggested that memory B cells needed to migrate to a specific lymphoid compartment in order to become fully responsive to antigenic stimulation in a T cell–independent way. To test this, we used TNF−/− and TNF/LTα−/− mice as recipients in which the organization of the lymphoid architecture is severely altered (20). Wild-type, TNF−/−, and TNF/LTα−/− C57BL/6 mice were treated with anti-CD4–specific antibody, and memory B cell preparations were adoptively transferred. An IgG memory response was clearly detectable in anti-CD4–treated wild-type mice, whereas only a minute IgG response was detected in TNF−/− recipients (Fig. 7). In TNF/LTα−/− recipients, the IgG memory response was completely absent, likewise in anti-CD4–treated C57BL/6 mice that had not received memory cells (Fig. 7). These results indicate that homing of memory B cells to secondary lymphoid tissue is required for the T cell–independent memory B cell response.

Bottom Line: Antigenic stimulation 4-6 d after transfer of B cells resulted in rapid IgG production.Transfer of memory B cells into immunocompetent animals indicated that presence of helper T cells did not enhance the memory B cell response.Therefore, our results indicate that activation of virus-specific memory B cells to secrete IgG is independent of cognate or bystander T cell help.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.

ABSTRACT
Humoral immunity is maintained by long-lived plasma cells, constitutively secreting antibodies, and nonsecreting resting memory B cells that are rapidly reactivated upon antigen encounter. The activation requirements for resting memory B cells, particularly the role of T helper cells, are unclear. To analyze the activation of memory B cells, mice were immunized with human cytomegalovirus, a complex human herpesvirus, and tick-born encephalitis virus, and a simple flavivirus. B cell populations devoid of Ig-secreting plasma cells were adoptively transferred into T and B cell-deficient RAG-1-/- mice. Antigenic stimulation 4-6 d after transfer of B cells resulted in rapid IgG production. The response was long lasting and strictly antigen specific, excluding polyclonal B cell activation. CD4+ T cells were not involved since (a) further depletion of CD4+ T cells in the recipient mice did not alter the antibody response and (b) recipient mice contained no detectable CD4+ T cells 90 d posttransfer. Memory B cells could not be activated by a soluble viral protein without T cell help. Transfer of memory B cells into immunocompetent animals indicated that presence of helper T cells did not enhance the memory B cell response. Therefore, our results indicate that activation of virus-specific memory B cells to secrete IgG is independent of cognate or bystander T cell help.

Show MeSH
Related in: MedlinePlus