High Proportion of CD5+ B Cells in Infants Predicts Development of Allergic Disease

Abstract

Delayed maturation of the immune system has been proposed to be a risk factor for development of allergy, but B cell maturation in relation to allergic disease has not been examined. B cells lose CD5 and acquire CD27 during maturation from immature via mature/naive to Ig-secreting cells and memory cells. We sought to investigate B cell maturation in relation to development of allergic disease and sensitization in the FARMFLORA birth cohort including 65 Swedish children. Total B cell numbers, proportions of CD5+ and CD27+ B cells, and levels of IgM, IgG, IgA, and IgE were measured in blood on repeated occasions from birth to 36 mo of age, and related to allergic disease and sensitization at 18 and 36 mo of age with multivariate discriminant analysis. We also compared the expression of CD24 and CD38 within CD5+ and CD5neg B cells in children and in adults. We found that infants with a high proportion of CD5+ B cells at birth and at 1 mo of age had an increased risk for having allergic disease at 18 and 36 mo of life. Further, the proportions of CD5+ B cells at 1 mo of age were inversely correlated with total IgG levels at 18 and 36 mo of age. The majority of the CD5+ B cells were of a CD24hi/+CD38hi/+ immature/naive phenotype at birth (97%), 7 y of age (95%), and in adults (86%). These results suggest that development of allergic disease is preceded by an immaturity in neonatal B cell phenotype.

Allergic disease in 8‐year‐old children is preceded by delayed B cell maturation

“…10 In accordance, adults with allergic asthma have higher proportions of immature/ transitional B cells (CD24 hi CD38 hi ) compared to healthy subjects. In the rural prospective FARMFLORA birth-cohort study, we have demonstrated that children with a high proportion of immature/na€ ıve CD5 + B cells during early infancy had a higher risk of developing allergic disease up to 3 years of age.…”

“…10,12,14 In the 8-year follow-up study, 48 children (74%; median age; 8.3 years, range 6.5-9.4) and their parents agreed to participate as shown in the participation flow diagram (Figure 1). In this region, rural areas are fairly similar with respect to population density and farming characteristics.…”

“…10,14 Thus, we next examined the incidence of allergic disease over the entire 8-year follow-up. 10,14 Thus, we next examined the incidence of allergic disease over the entire 8-year follow-up.…”

Antibiotics, Pediatric Dysbiosis, and Disease

“…As mentioned previously, normal development of the immune system is dependent on key members of the gut microbiome for the development of regulatory components of the immune system as well as maintaining homeostasis at the gut epithelium. Allergic and atopic disorders are primarily caused by impaired components of the adaptive immune system that rely largely on the gut microbiome (Fujimura and Lynch 2015): for example, B cell maturity (Lundell et al, 2014) and regulatory T cell differentiation and expansion (Atarashi et al, 2013). Distinct compositions of infant gut microbiomes have been associated with the development of atopic diseases later in life (Abrahamsson et al, 2012; Atarashi et al, 2013; Bisgaard et al, 2011; Björkstén et al, 2001), and therefore it is conceivable that early exposure to antibiotics, especially broad-spectrum antibiotics, could be responsible for shaping the gut microbiome with predisposition toward allergy and atopic diseases.…”

The Developing Immune System and Allergy

“…178 CD40L represents a critical signal for T helper cell-induced class switching 179 and the generally low expression on neonatal T cells may thus be a limiting factor in the process. 181 Growing interest in the human microbiome in health and disease has reawakened interest in the role of gut flora in the development of the overall B cell repertoire, 182 in particular the stimulatory effect of early gut colonization on B memory cell expansion. However, although immunoglobulin production by neonatal B cells is low in the presence of neonatal T helper cells, production levels can be markedly improved if mature T helper cells or adequate soluble signals are provided.…”