A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people

Abstract

The T cell branch of the immune system has been extensively studied in the elderly and it is known that the elderly have impaired immune function, mainly due to the chronic antigenic load that ultimately causes shrinkage of the T cell repertoire and filling of the immunologic space with memory T cells. In the present paper, we describe the IgD(-)CD27(-) double-negative B cell population which (as we have recently described) is higher in the elderly. Most of these cells were IgG(+). Evaluation of the telomere length and expression of the ABCB1 transporter and anti-apoptotic molecule, Bcl2, shows that they have the markers of memory B cells. We also show that these cells do not act as antigen presenting cells, as indicated by the low levels of CD80 and DR, nor do they express significant levels of the CD40 molecule necessary to interact with T lymphocytes through the ligand, CD154. Hence, we hypothesize that these expanded cells are late memory or exhausted cells that have down-modulated the expression of CD27 and filled the immunologic space in the elderly. These cells might be the age-related manifestation of time-enduring stimulation or dysregulation of the immune system.

B cell immunosenescence: different features of naive and memory B cells in elderly

“…This leads us to the hypothesis that there is a large population of DN cells that are unrelated to classical memory B cells. The increase of the double negative memory B cells in the elderly (Colonna-Romano et al 2009;Bulati et al 2011), together with the reduced rate of mutation shown here, might be due to the disconnected generation of these cells from germinal centers, as it has been demonstrated that ageing negatively affects the germinal center formation in secondary lymphoid tissues (William et al 2002;Frasca et al 2005).From this and our previous papers (Colonna-Romano et al 2009 we can conclude that DN B lymphocytes are exhausted cells. In fact they are not activated by anti-CD40/IL4, or by CpG/PMA/Ionomycin and behave differently as CMV-specific effector-memory CD8 lymphocytes.…”

“…In a previous paper we have reported the increase in a population of double negative, IgD -CD27 -, (DN) B cells in the elderly that might be an exhausted pool of memory B cells that fill the immunological B cell space (Colonna-Romano et al 2009), thus reducing the availability of naïve B cells that is crucial for a response to new antigens. Moreover, naïve and memory B cells produce different pro-and anti-inflammatory cytokines (Duddy et al 2004;Duddy et al 2007;Sanz et al 2007Sanz et al , 2008Lund 2008) and might play a role in the generation of the inflammatory environment typical of the elderly (Licastro et al 2005;Vasto et al 2007).…”

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

“…32,33 Thus a possible explanation for the loss of long-term memory in patients with CGD can be an ineffective polyclonal activation of memory B cells, which usually maintain serologic memory. 28,34,35 However, we also found numbers of CD27/IgD double-negative B cells, which were previously described as increased in elderly healthy subjects, 36 HIV-infected children, and patients undergoing kidney transplantation, 37 to be higher among patients with CGD compared with those seen in HCs. This might support the hypothesis that B cells from patients with CGD could also be unresponsive to stimuli because of premature aging.…”

Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity

“…The function of DN B cells, however, is poorly defined. DN B cells are elevated in the elderly and in inflammatory diseases including established RA, SLE, and Alzheimer's disease, suggesting their contribution to pathology in disease and in immune changes associated with aging (8,11,109,110). There are several hypotheses on the origin of DN B cells including that they are exhausted memory B cells that have downregulated CD27 (109), memory B cell precursors that have not acquired CD27 yet (111), or an entirely new B cell population that has undergone low levels of somatic hypermutation (111,112).…”