Differences in mouse and human nonmemory B cell pools.

Identifying cross-species similarities and differences in immune development and function is critical for maximizing the translational potential of animal models. Coexpression of CD21 and CD24 distinguishes transitional and mature B cell subsets in mice. In this study, we validate these markers for identifying analogous subsets in humans and use them to compare the nonmemory B cell pools in mice and humans, across tissues, and during fetal/neonatal and adult life. Among human CD19(+)IgM(+) B cells, the CD21/CD24 schema identifies distinct populations that correspond to transitional 1 (T1), transitional 2 (T2), follicular mature, and marginal zone subsets identified in mice. Markers specific to human B cell development validate the identity of marginal zone cells and the maturation status of human CD21/CD24 nonmemory B cell subsets. A comparison of the nonmemory B cell pools in bone marrow, blood, and spleen in mice and humans shows that transitional B cells comprise a much smaller fraction in adult humans than mice. T1 cells are a major contributor to the nonmemory B cell pool in mouse bone marrow, in which their frequency is more than twice that in humans. Conversely, in spleen, the T1:T2 ratio shows that T2 cells are proportionally ∼ 8-fold higher in humans than in mice. Despite the relatively small contribution of transitional B cells to the human nonmemory pool, the number of naive follicular mature cells produced per transitional B cell is 3- to 6-fold higher across tissues than in mice. These data suggest differing dynamics or mechanisms produce the nonmemory B cell compartments in mice and humans.

Colorectal cancer in middle-aged women in relation to hormonal status: a report from the Women's Health in the Lund Area (WHILA) study.

OBJECTIVE: To delineate a perceived association of estradiol versus estradiol plus norethisterone hormone therapy on the prevalence of colorectal cancer in postmenopausal women. METHODS: The Women's Health in the Lund Area (WHILA) project covers 10,766 women aged 50-60 years, living in the Lund area, Sweden. Out of this population, 6908 (64%) women completed questionnaires, underwent physical and laboratory assessments and had self-reported information regarding colorectal cancer. Four hundred and twenty-two (6%) were premenopausal (PM), 3600 (52%) were postmenopausal without hormone therapy (PM0), 2452 (36%) were postmenopausal with combined hormone therapy (PMT-HT) and 364 (5%) were postmenopausal with estrogen monotherapy (PMT-E). RESULTS: There were 21 cases of colorectal cancer (0.3%), one in the PM group, 16 in the PM0 group, two in the PMT-HT group and another two in the PMT-E group. Colorectal cancer prevalence was lower in the PMT-HT than in the PM0 group (odds ratio (OR) = 0.18, 95% confidence interval (CI) = 0.04-0.80). However, for the PMT-E group, the OR (95% CI) was 1.02 (0.86-1.20). There was a positive association between low physical activity (p = 0.04), low parity (p = 0.02) and risk of colorectal cancer. CONCLUSION: Combined hormone therapy seemed to be associated with a lower risk of colorectal cancer in postmenopausal women in contrast to estrogen monotherapy. Hence the progestin might have a protective role.