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

Whether CD5 on B cells marks a subset functionally distinct from the conven tional CD5 negative (CD5(neg)) adult population or is more an indicator of activation, remains contentious. Here we have investigated whether CD5 posi tive (CD5(pos)) and CD5(neg) 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 predominant ly CD5(pos) B-cell population found in cord blood, CD5 B cells positively s elected from tonsils and their CD5(neg) counterparts, were compared. Neonat al B cells displayed a near-identical phenotype to that of adult CD5(pos) B cells, being characterized by uniform immunoglobulin M (IgM), immunoglobul in D (IgD), CD23 and CD44 coexpression. When cultured with anti-IgM maintai ned 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-Ig M) to model TD encounters, DNA synthesis was stimulated to a similar extent in all three populations. Focusing on CD5 and CD23, we found that - althou gh the signals delivered promoted distinct profiles of expression - under e ach condition of activation, the phenotypes that emerged for adult CD5(pos) and CD5(neg) B cells were remarkably similar. Neonatal B cells displayed a greater diminution in CD5 expression than adult CD5(pos) B cells following CD40 signals but otherwise the two populations again behaved similarly. Th e inclusion of interleukin-4 (IL-4) to cultures where cells were costimulat ed via surface (s)IgM and CD40 resulted in a complete loss of CD5 expressio n and a corresponding hyperexpression of CD23, irrespective of the populati on studied. The near-identical response of CD5(pos) and CD5(neg) B cells to surrogate TD or TI signals in vitro and their convergence to indistinguish able phenotypes is wholly supportive of CD5 being a fluctuating marker of a ctivation rather than it delineating functionally distinct subsets.