Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer/IBMCC (CSIC-USAL), Salamanca, Spain.
Cytometry B Clin Cytom. 2010;78 Suppl 1:S24-34. doi: 10.1002/cyto.b.20543.
Monoclonal B-cell lymphocytosis (MBL) indicates <5 × 10(9) peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells-CLL-like MBL-but little is known about non-CLL-like MBL.
PB samples from 639 healthy individuals (46% men/54% women) >40 years old (62 ± 13 years) with normal lymphocyte counts (2.1 ± 0.7 × 10(9)/L) were immunophenotyped using high-sensitive flow cytometry, based on 8-color stainings and the screening for >5 × 10(6) total PB leukocytes.
Thirteen subjects (2.0%; 9 males/4 females, aged 73 ± 10 years; absolute lymphocyte count: 2.4 ± 0.8 × 10(9)/L) showed a non-CLL-like clonal B-cell population, whose frequency clearly increased with age: 0.4%, 3%, and 5.4% of subjects aged 40-59, 60-79, and ≥80 years, respectively. One single B-cell clone was detected in 9/13 cases, while two B-cell clones were found in 4/13 (n = 17 MBL populations). Nine MBL cell populations showed a CD5(-) phenotype (usually overlapping with marginal zone-derived (MZL) or lymphoplasmacytic (LPL) non-Hodgkin lymphoma (NHL) B-cells, or an unclassifiable NHL), but CD5(-/+d) (n = 3) and CD5(+) (n = 3 non-CLL-like MBL, consistent with a mantle-cell lymphoma (MCL)-like phenotype, and n = 2 CLL-like) MBL were also identified; iFISH supported the diagnosis in most cases. No preferential IGHV usage of B-cell receptor could be found. Twelve cases reevaluated at month +12 showed circulating clonal B-cells, at mean levels significantly higher than those initially detected.
Non-CLL-like MBL cases frequently show biclonality, in association with MZL-, LPL-, MCL-like, or unclassifiable phenotypic profiles. As with CLL-like MBL, the frequency of non-CLL-like MBL increases with age, with a clear predominance of males.
单克隆 B 细胞淋巴增生症(MBL)是指健康个体外周血(PB)中克隆性 B 细胞<5×10(9)/L。在大多数情况下,MBL 细胞表现出与慢性淋巴细胞白血病细胞(CLL 样 MBL)相似的表型/遗传学特征,但对非 CLL 样 MBL 知之甚少。
对 639 名年龄>40 岁(62±13 岁)、淋巴细胞计数正常(2.1±0.7×10(9)/L)的健康个体的 PB 样本进行免疫表型分析,采用高敏感流式细胞术,基于 8 色染色,并筛选出>5×10(6)个总 PB 白细胞。
13 例(2.0%;9 男/4 女,年龄 73±10 岁;绝对淋巴细胞计数:2.4±0.8×10(9)/L)表现出非 CLL 样克隆性 B 细胞群体,其频率随年龄明显增加:40-59 岁、60-79 岁和≥80 岁的受试者分别为 0.4%、3%和 5.4%。9/13 例检测到单个 B 细胞克隆,4/13 例发现 2 个 B 细胞克隆(n=17 MBL 群体)。9 个 MBL 细胞群表现为 CD5(-)表型(通常与边缘区衍生(MZL)或淋巴浆细胞(LPL)非霍奇金淋巴瘤(NHL)B 细胞重叠,或无法分类的 NHL),但也发现了 CD5(-/+d)(n=3)和 CD5(+)(n=3 例非 CLL 样 MBL,符合套细胞淋巴瘤(MCL)样表型,n=2 例 CLL 样)MBL;荧光原位杂交(iFISH)在大多数病例中支持诊断。未发现 B 细胞受体的 IGHV 偏好性使用。12 例在+12 个月时重新评估的病例显示循环克隆性 B 细胞,其水平明显高于最初检测到的水平。
非 CLL 样 MBL 病例常表现为双克隆性,与 MZL、LPL、MCL 样或无法分类的表型谱相关。与 CLL 样 MBL 一样,非 CLL 样 MBL 的频率随年龄增加而增加,且男性明显居多。