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Burst-enhancing role of the IgG membrane tail as a molecular determinant of memory

Nature Immunology volume 3, pages 182–188 (2002)Cite this article

Abstract

The basis of immune memory leading to heightened secondary antibody responses is a longstanding unanswered issue. Here we show that a single irreversible molecular change in the B cell antigen receptor, which is brought about by immunoglobulin M (IgM) to IgG isotype switching, is sufficient to greatly increase the extrafollicular proliferative burst of antigen-specific B cells. The unique membrane-spanning regions of IgG do not alter the T cell–dependent activation and proliferation of antigen-specific B cells in vivo, but markedly increase the number of progeny cells and plasmablasts that accumulate. These results establish a key molecular determinant of immunological memory and define an unexpected cellular basis by which it enhances the magnitude of secondary antibody responses.

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Figure 1: Seeding a primary antibody response with naïve B cells bearing high-affinity receptors confers memory-response characteristics when the receptors contain the unique IgG membrane tail.
Figure 2: The IgG membrane tail augments the production of AFCs.
Figure 3: The IgG membrane tail augments clonal expansion.
Figure 4: Heightened antibody responses by IgG and IgMG cells are independent of developmental state or other BCR specificities.
Figure 5: Heightened response is due to the membrane tail of IgG, not Tg line-to-line variation.
Figure 6: Burst-enhancing effect of the IgG membrane tail acts by reducing cell attrition.
Figure 7: The IgG-enhanced response occurs in the normal perifollicular and extrafollicular locations.

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Acknowledgements

We thank K. Sullivan and the staff of the Medical Genome Centre for expert care and breeding of the transgenic mice and L. Wilson and A. Murtagh for expert genotyping.

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Authors and Affiliations

  1. ACRF Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Australian National University, PO Box 334, Mills Road, Canberra, 2601, Australia

    Stephen W. Martin & Christopher C. Goodnow

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  2. Christopher C. Goodnow
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Correspondence to Christopher C. Goodnow.

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The authors declare no competing financial interests.

Supplementary information

Web Figure 1.

Construct information and membrane tail BCR sequence from the various anti-HEL Ig–Tg lines used. Information is taken from descriptions of the MD423; MM422; MG2, MG6 and GG424 Tg lines and from a description of the constructs used to produce the MδE1 and MδE2 Tg lines26. LVDJ, rearranged variable region genes from the antiHEL hybridoma HyHEL10; Eμ, μ intronic enhancer; SR μ, intact μ switch region; SR μ*, μ switch region carrying a 2.8-kb internal deletion; SR μ/g, hybrid switch region between μ and g. Dashes indicate sequence identity with the μ Hc. (GIF 31 kb)

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Martin, S., Goodnow, C. Burst-enhancing role of the IgG membrane tail as a molecular determinant of memory. Nat Immunol 3, 182–188 (2002). https://doi.org/10.1038/ni752

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