CD23 and immune modulation We read with interest the recent article by Mudde and colleagues (Immunol. Today, 1990, 11, 440443), speculating on a special role for IgE in antigen presentation. However, the emphasis may have been placed on the wrong molecule as the 'capture of antigen' is surely a feature of all classes of immunoglobulin, not just IgE! On the other hand, CD23 - which can bind IgE with low affinity - may well contribute to the presentation of antigen by B cells and, perhaps, other cells 1. CD23 is spatially linked to major histocompatibility complex (MHC) class II DR 2 and ligands binding within its lectin-homology domain suppress the antigen-presenting capacity of B cells3,4. Importantly, the switching of uncommitted B cells to the production of IgE minimally requires (1) physical contact with CD4 + cells via MHC class H molecules and the T-cell receptor, and (2) the interleukin 4 (IL-4) that is subsequently produced 5. We have postulated that interrupting these essential early events by surplus IgE binding to CD23 could provide negative feedback on IgE production in an ongoing response4: where antigen remained in excess, positive feedback would ensue after the internalization of IgE-antigen complexes. Rather than simply providing an anchor for IgE, we view CD23 functioning directly as an accessory molecule during antigen presentation by B cells. Indeed, soluble CD23 is co-mitogenic for CD4 ÷ T cells (Ref. 6 and J.M. Bertho etal., unpublished), while the de novo expression of membrane CD23 promotes intercellular adhesions among previously nonadherent cells 7. The most striking expression of CD23 is associated with a subset of follicular dendritic cells (FDCs) and we have suggested a role for FDCassociated CD23 in the development of germinal centre B cells 1. There is no evidence that FDCs process antigen; yet, in pursuit of their thesis, Mudde and colleagues seemed prepared to dismiss a large body of work on the B-lymphotropic properties of CD23 by citing a single reference where bacterial-derived

recombinant material was apparently inactive in a standard 'BCGF' assay 8. Recent studies demonstrate that - in synergy with IL-1 recombinant 25 kDa CD23 derived from insect cells assists the survival of germinal centre B cells and promotes their morphological differentiation (Y-J. Liu et al., unpublished). Such synergistic activity for recombinant CD23 and IL-1 has also been noted for the differentiation of immature thymocytes and CD34 + myeloid precursors 9,1°. The role of the low-affinity IgE receptor in antigen presentation is clearly a fascinating area which deserves further study. The accumulated data, however, suggest that this molecule is important not only in the regulation of IgE synthesis but also in mechanisms of lymphocyte and monocyte differentiation that are quite independent of IgE.

John Gordon Yong-Jun Liu Ian C.M. MacLennan Dept of Immunology, The Medical School, Vincent Drive, Birmingham B15 2TT, UK. Leopoldo Flores-Romo

John Shields

Jean-Yves Bonnefoy Glaxo Institute for Molecular Biology SA, Route des Acacias 46, CH-1211 Geneva 24, Switzerland.

References 1 Gordon, J., Flores-Romo, L., Cairns, J.A. et al. (1989) Immunol. Today 10, 153-157 2 Bonnefoy, J-Y., Buillot, O., Spits, H. et al. (1988)J. Exp. Med. 167, 57-65 3 Flores-Romo, L., Wallace, L. and Gordon, J. (1989) in Leucocyte Typing IV (Knapp, W. et al., eds), p. 77, Oxford University Press 4 Flores-Romo, L., Johnson, G.D., Ghaderi, A.A. et al. (1990) Eur. J. Immunol. 20, 2465-2469 5 Vercelli, D.H., Jabara, H., Arai, K-I. and Geha, R.S. (1989) J. Exp. Med. 169, 1295-1307 6 Armitage, R.J., Goff, L.K. and Beberley, P.L.C. (1989) Eur. J. Immunol. 19, 31-37 7 Kikutani, H., Yokota, A., Uchibayashi, N. et al. (1989) in IgE, Mast Cells, and the Allergic Response (Ciba Foundation Symposium), p. 23, John Wiley 8 Uchibayashi, N., Kikutani, H. and Barsumian, E.L. (1989) J. Immunol. 142, 3901-3908 9 Mossalayi, M.D., Lecron, J.C., Dalloul, A.H. et al. (1990) J. Exp. Med. 171, 1959-1963 10 Mossalayi, M.D., Arock, M., Bertho, J.M. et al. (1990) Blood 75, 1924-1928

Reply We thank John Gordon and colleagues for their interesting letter, providing novel insights into roles for CD23 in the regulation of IgE responses and germinal centre B-cell survival and differentiation. However, our rostrum article was not intended to be an all-embracing essay on the action of CD23, but rather to speculate on a role for IgE in antigen capture. The following points answer specific criticisms on this latter theme. (1) In our paper we devoted the section 'IgG is not used for antigen capture' to explaining why we think IgG does not have a role in antigen capture in the context of antigen processing and presentation. (2) We are fully aware that there is no evidence for antigen processing by follicular dendritic cells, and we

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were careful not to claim this in our article. (3) When there is controversy over the function of a particular protein, assay of this protein in recombinant form can be especially informative. For this reason we stressed the fact that recombinant soluble CD23 from a bacterial vector had IgEbinding properties but no BCGF activity. Since recombinant CD23 from an insect vector assists the survival and morphological differentiation of germinal centre B cells, we eagerly await confirmation of the BCGF activity of this preparation.

Vol. 12 No. 6 1991

Geert Mudde Trevor Hansel Swiss Institute for Allergy and Asthma Research (SIAF), Davos, Switzerland.