CD5‐positive and CD5‐negative human B cells converge to an indistinguishable population on signalling through B‐cell receptors and CD40

A Gagro, N McCloskey, A Challa, M Holder… - …, 2000 - Wiley Online Library
A Gagro, N McCloskey, A Challa, M Holder, G Grafton, JD Pound, J Gordon
Immunology, 2000Wiley Online Library
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 …
Summary
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.
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