Present addresses: The Randall Centre for Molecular Mechanisms of Cell Function, GKT School of Biomedical Sciences, London, UK, §Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, UK.
CD5-positive and CD5-negative human B cells converge to an indistinguishable population on signalling through B-cell receptors and CD40
Article first published online: 25 DEC 2001
Volume 101, Issue 2, pages 201–209, October 2000
How to Cite
Gagro, A., Mccloskey, N., Challa, A., Holder, M., Grafton, G., Pound, J. D. and Gordon, J. (2000), CD5-positive and CD5-negative human B cells converge to an indistinguishable population on signalling through B-cell receptors and CD40. Immunology, 101: 201–209. doi: 10.1046/j.1365-2567.2000.00098.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Received 3 March 2000; revised 25 May 2000; accepted 9 June 2000.
Whether CD5 on B cells marks a subset functionally distinct from the conventional CD5 negative (CD5neg) adult population or is more an indicator of activation, remains contentious. Here we have investigated whether CD5 positive (CD5pos) and CD5neg B cells can be distinguished in terms of their response to surrogate signals aimed to model, in vitro, T-cell dependent (TD) and T-independent (TI) encounters with antigen in vivo: the predominantly CD5pos B-cell population found in cord blood, CD5 B cells positively selected from tonsils and their CD5neg counterparts, were compared. Neonatal B cells displayed a near-identical phenotype to that of adult CD5pos B cells, being characterized by uniform immunoglobulin M (IgM), immunoglobulin D (IgD), CD23 and CD44 coexpression. When cultured with anti-IgM maintained at high density on CD32-tranfected mouse L cells to model TI responses or on CD40 ligand (CD40L)-bearing L cells (with or without captured anti-IgM) to model TD encounters, DNA synthesis was stimulated to a similar extent in all three populations. Focusing on CD5 and CD23, we found that – although the signals delivered promoted distinct profiles of expression – under each condition of activation, the phenotypes that emerged for adult CD5pos and CD5neg B cells were remarkably similar. Neonatal B cells displayed a greater diminution in CD5 expression than adult CD5pos B cells following CD40 signals but otherwise the two populations again behaved similarly. The inclusion of interleukin-4 (IL-4) to cultures where cells were costimulated via surface (s)IgM and CD40 resulted in a complete loss of CD5 expression and a corresponding hyperexpression of CD23, irrespective of the population studied. The near-identical response of CD5pos and CD5neg B cells to surrogate TD or TI signals in vitro and their convergence to indistinguishable phenotypes is wholly supportive of CD5 being a fluctuating marker of activation rather than it delineating functionally distinct subsets.