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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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Antibody responses after adoptive transfer of memory B and memory T cells. C57BL/6 mice received 5 × 106 B cells from C57BL/6 mice immunized with HCMV-DBs (○), 5 × 106 immune B cells together with 5 × 106 CD4+ T cells from C57BL/6 mice previously immunized with HCMV-DBs (•) or no cells (▪). On day 6 posttransfer, the mice were challenged with 2 μg HCMV-DBs i.v. Blood was taken at the days indicated, and sera were analyzed by ELISA for HCMV-specific IgG. The values represent the mean values (± SD) of four recipient mice, and one of two similar experiments is shown.
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fig4: Antibody responses after adoptive transfer of memory B and memory T cells. C57BL/6 mice received 5 × 106 B cells from C57BL/6 mice immunized with HCMV-DBs (○), 5 × 106 immune B cells together with 5 × 106 CD4+ T cells from C57BL/6 mice previously immunized with HCMV-DBs (•) or no cells (▪). On day 6 posttransfer, the mice were challenged with 2 μg HCMV-DBs i.v. Blood was taken at the days indicated, and sera were analyzed by ELISA for HCMV-specific IgG. The values represent the mean values (± SD) of four recipient mice, and one of two similar experiments is shown.

Mentions: Finally, we wanted to analyze a potential enhancing effect of virus-specific memory T cells on virus-specific memory B cell responses by an adoptive cotransfer of CD4+ helper T cells into RAG-1−/− mice. However, a rapid and dramatic inflammatory bowel disease developing after the transfer of sorted CD4+ cells into syngeneic C57BL/6 RAG-1−/− mice prevented the analysis of the influence of CD4+ cells in the adoptive transfer experiments involving RAG-1−/− mice. For this reason, we decided to adoptively transfer B cells from HCMV-DB–immunized C57BL/6 mice into naive C57BL/6 mice with or without CD4+ T cells from the spleen and lymph node of HCMV-DB–immunized mice as a source of primed T cell help. As expected, the challenge of recipient and control mice with HCMV-DBs yielded faster IgG antibody responses with higher titer in recipients of sorted B cells containing virus-specific memory B cells when compared with naive control mice. Naive C57BL/6 mice responded to a single i.v. immunization with HCMV-DBs since the mice were not irradiated (Fig. 4). Importantly, the transfer of CD4+ cells from HCMV-DB–immunized C57BL/6 mice together with sorted B cells did not enhance the virus-specific antibody response in the recipient mice (Fig. 4).


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)

Antibody responses after adoptive transfer of memory B and memory T cells. C57BL/6 mice received 5 × 106 B cells from C57BL/6 mice immunized with HCMV-DBs (○), 5 × 106 immune B cells together with 5 × 106 CD4+ T cells from C57BL/6 mice previously immunized with HCMV-DBs (•) or no cells (▪). On day 6 posttransfer, the mice were challenged with 2 μg HCMV-DBs i.v. Blood was taken at the days indicated, and sera were analyzed by ELISA for HCMV-specific IgG. The values represent the mean values (± SD) of four recipient mice, and one of two similar experiments is shown.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: Antibody responses after adoptive transfer of memory B and memory T cells. C57BL/6 mice received 5 × 106 B cells from C57BL/6 mice immunized with HCMV-DBs (○), 5 × 106 immune B cells together with 5 × 106 CD4+ T cells from C57BL/6 mice previously immunized with HCMV-DBs (•) or no cells (▪). On day 6 posttransfer, the mice were challenged with 2 μg HCMV-DBs i.v. Blood was taken at the days indicated, and sera were analyzed by ELISA for HCMV-specific IgG. The values represent the mean values (± SD) of four recipient mice, and one of two similar experiments is shown.
Mentions: Finally, we wanted to analyze a potential enhancing effect of virus-specific memory T cells on virus-specific memory B cell responses by an adoptive cotransfer of CD4+ helper T cells into RAG-1−/− mice. However, a rapid and dramatic inflammatory bowel disease developing after the transfer of sorted CD4+ cells into syngeneic C57BL/6 RAG-1−/− mice prevented the analysis of the influence of CD4+ cells in the adoptive transfer experiments involving RAG-1−/− mice. For this reason, we decided to adoptively transfer B cells from HCMV-DB–immunized C57BL/6 mice into naive C57BL/6 mice with or without CD4+ T cells from the spleen and lymph node of HCMV-DB–immunized mice as a source of primed T cell help. As expected, the challenge of recipient and control mice with HCMV-DBs yielded faster IgG antibody responses with higher titer in recipients of sorted B cells containing virus-specific memory B cells when compared with naive control mice. Naive C57BL/6 mice responded to a single i.v. immunization with HCMV-DBs since the mice were not irradiated (Fig. 4). Importantly, the transfer of CD4+ cells from HCMV-DB–immunized C57BL/6 mice together with sorted B cells did not enhance the virus-specific antibody response in the recipient mice (Fig. 4).

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