Imbalance between inflammatory and regulatory cord blood B cells following pre-term birth

Area of Science:

• Immunology
• Neonatology
• Perinatology

Background:

• Preterm birth (PTB) is a major complication affecting millions of newborns globally, linked to increased mortality and morbidity.
• Maternal immune system alterations during PTB may impact fetal immune development.
• Previous research indicated reduced and impaired B regulatory (Breg) cells in maternal blood of women with PTB.

Purpose of the Study:

• To investigate adaptive immune system alterations in cord blood (CB) following PTB.
• To determine if PTB affects B cell populations and their regulatory functions in the fetal compartment.

Main Methods:

• Analysis of cord blood (CB) and amniotic fluid (AF) from PTB and term delivery (TD) cohorts.
• Flow cytometry to assess frequencies of B cells, T cells, T regulatory cells, and Breg cells (CD24hiCD38hi, CD1dhiCD5+).
• Measurement of cytokine concentrations (IL-6, TNF-α, IL-21, IFN-γ, IL-4, IL-9, IL-2) in CB and AF.

Main Results:

• PTB was associated with increased IL-6, TNF-α, and IL-21 in CB, and elevated IL-6 but reduced IFN-γ and IL-4 in AF compared to TD.
• Frequencies of CD19+ B cells, CD4+ T cells, and CD4+Foxp3+CD25+ T regulatory cells in CB did not differ between PTB and TD.
• PTB showed increased CD86+ B cells, decreased Breg cell percentages, and impaired B cell conversion to Breg cells. CB B cells from PTB infants secreted higher levels of inflammatory cytokines (IL-6, TNF-α, IL-9, IL-2).

Conclusions:

• PTB onset induces a shift from immunoregulation to inflammation in fetal cord blood, with significant B cell involvement.
• These immune alterations in the fetal compartment may contribute to the higher mortality and morbidity observed in preterm infants.
• Further research could utilize CB immune profiling for monitoring high-risk newborns.