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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 different host mice lacking functional CD4+ cells. 5 × 106 sorted B cells from hyperimmunized C57BL/6 mice were transferred as described in Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. The IgG antibody response in different recipient mice was measured 7 d after challenge with 2 μg HCMV-DBs i.v. Controls received no memory B cell preparations. The bars represent the mean of RI values; dots are individual values.
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fig2: IgG memory response in different host mice lacking functional CD4+ cells. 5 × 106 sorted B cells from hyperimmunized C57BL/6 mice were transferred as described in Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. The IgG antibody response in different recipient mice was measured 7 d after challenge with 2 μg HCMV-DBs i.v. Controls received no memory B cell preparations. The bars represent the mean of RI values; dots are individual values.

Mentions: In RAG-1−/− mice, a homeostatic expansion of a fraction of B cells has been observed, which show an activated phenotype (14). To exclude potential influences of the complete lack of competition in the RAG-1−/− system, we used additional experimental settings. In a first set of experiments, we used TCRβ/δ−/− mice devoid of any T lymphocytes (15) as recipients for adoptively transferred memory B cells from HCMV-DB–immunized C57BL/6 animals. These mice reacted equally well to antigenic stimulation with HCMV-DBs as RAG-1−/− recipients (Fig. 2). In a second set of experiments, immunocompetent C57BL/6 mice were treated with the monoclonal antibody GK1.5 to eliminate endogenous CD4+ T cells. These mice were then used as hosts for memory B cells from HCMV-DB–immunized donors. Recipient mice were stimulated with antigen on day 1 after transfer. Whereas GK1.5 antibody treatment completely prevented an IgG response against HCMV-DBs, it allowed production of IgG in animals that had received memory B cells (Fig. 2). Thus, the T cell–independent memory B cell response that we observe in RAG−/− recipients is not a consequence of B cell expansion and homeostatic differentiation.


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 different host mice lacking functional CD4+ cells. 5 × 106 sorted B cells from hyperimmunized C57BL/6 mice were transferred as described in Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. The IgG antibody response in different recipient mice was measured 7 d after challenge with 2 μg HCMV-DBs i.v. Controls received no memory B cell preparations. The bars represent the mean of RI values; dots are individual values.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211828&req=5

fig2: IgG memory response in different host mice lacking functional CD4+ cells. 5 × 106 sorted B cells from hyperimmunized C57BL/6 mice were transferred as described in Fig. 1, and mice were challenged with antigen 1 d after adoptive transfer of cells. The IgG antibody response in different recipient mice was measured 7 d after challenge with 2 μg HCMV-DBs i.v. Controls received no memory B cell preparations. The bars represent the mean of RI values; dots are individual values.
Mentions: In RAG-1−/− mice, a homeostatic expansion of a fraction of B cells has been observed, which show an activated phenotype (14). To exclude potential influences of the complete lack of competition in the RAG-1−/− system, we used additional experimental settings. In a first set of experiments, we used TCRβ/δ−/− mice devoid of any T lymphocytes (15) as recipients for adoptively transferred memory B cells from HCMV-DB–immunized C57BL/6 animals. These mice reacted equally well to antigenic stimulation with HCMV-DBs as RAG-1−/− recipients (Fig. 2). In a second set of experiments, immunocompetent C57BL/6 mice were treated with the monoclonal antibody GK1.5 to eliminate endogenous CD4+ T cells. These mice were then used as hosts for memory B cells from HCMV-DB–immunized donors. Recipient mice were stimulated with antigen on day 1 after transfer. Whereas GK1.5 antibody treatment completely prevented an IgG response against HCMV-DBs, it allowed production of IgG in animals that had received memory B cells (Fig. 2). Thus, the T cell–independent memory B cell response that we observe in RAG−/− recipients is not a consequence of B cell expansion and homeostatic differentiation.

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