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Faculty have requested this content not be shared on social media
CME Credit Offered
CME Credit Offered
Abstract Award
Abstract Award
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Poster Session 2

(472) Determining the role of pregnancy-induced alterations to B cells in decreasing risk for breast cancer

Thursday, January 30, 2025
4:00 PM – 6:00 PM  
Objective: An early age of first pregnancy ( < 25 years) decreases the lifelong risk of developing breast cancer (BC). This study characterizes how B cells that infiltrate the gland during pregnancy and lactation may play a role in preventing BC.
 

 

 

 

 

 

Study Design: Wildtype female mice and a mouse model of Brca1 loss (Krt5CRE-ERT2Brca1fl/flp53+/-) were used in this study. Single-cell RNA-seq (scRNA-seq) datasets were generated from mammary tissue of nulliparous and parous mice with Brca1 loss without tumors. B cell receptor (BCR)-seq datasets were generated from nulliparous and parous wildtype mice. Differential gene expression and clustering analyses were performed using the R pipeline Seurat. Clonotype analysis and extraction of BCR sequences were performed using Loupe V(D)J Browser by 10X Genomics. Recombinant post-pregnancy mammary IgG antibodies were synthesized by the CSHL Antibody & Phage Display Core Facility and tested by immunofluorescent (IF) staining.
 

 

 

 

 

 

Results: scRNA-seq analysis showed that parous mice with Brca1 loss have an expansion of antibody-secreting B cells in their mammary glands (MGs), suggesting that B cells that infiltrate the MG during pregnancy remain there and may secrete antibodies that inhibit mammary tumor formation. To analyze these B cells on a clonal level, we analyzed BCR-seq data to identify the most abundant IgG clones unique to the parous MG. We extracted the sequences of these clones and used them to synthesize recombinant IgG antibodies. Using IF staining of mammary tissue from healthy mice (nulliparous, pregnant, and parous) and mice with mammary pre-neoplasia, we found that post-pregnancy IgG antibodies recognize antigens induced by pregnancy and lactation that are also present in mammary pre-neoplastic tissue. We are currently testing these antibodies in our mouse model of Brca1 loss to evaluate their ability to block mammary tumor development.
 

 

 

 

 

 

Conclusion: In addition to their role in secreting antibodies into breastmilk that confer immunity to the nursing infant, our results suggest a role for pregnancy-induced antibody-secreting B cells in long-term breast oncoprotection.