Preferential expression of IGHV and IGHD encoding antibodies with exceptionally long CDR3H and a rapid global shift in transcriptome characterizes development of bovine neonatal immunity

Abstract

With an objective to understand natural development of bovine neonatal immunity, we analyzed 18 RNA-seq libraries from peripheral blood lymphocytes of three neonatal calves pre- (day 0) and post-colostrum (7, 14 and 28) uptake as compared to their dams. A significant global shift in neonatal transcriptome occurs within first week post-birth, in contrast to dams, with an upregulation of 717 genes. Global pathway analysis of the transcriptome revealed 110 differentially expressed immune-related genes, such as, complement, MHCII, chemokine receptors, defensins and cytokines, at birth. The signaling molecules (LAX1, BLK) and transcription factors (GATA3, FOXP3) are expressed at high levels. High expression of GATA3 transcription factor at birth seems to skew the neonatal immune response towards TH2 type. The high levels of T-cell signaling molecules, CD3G and CD3D, at birth are important in neonatal T cell development. Unlike adults, IGKC expression is high in the neonates where IGKV12 is preferentially expressed at birth. But IGLC is predominant in both neonates and adult where IGLV3.4 is preferentially expressed in B cells at birth. Both IGHM and IGHD are expressed at birth and IGHM achieves adult levels by day 7. This is followed by IGHA and IGHG expression 14–28 days post-birth. Importantly, preferential expression of IGHV1S1(BF4E9) and longest IGHD2(DH2) genes that encode immunoglobulin with exceptionally long CDR3H at birth indicates their critical role, as B cell antigen receptor, in the B cell development via idiotype-anti-idiotype interactions. The transcriptome signatures described here permit assessment bovine neonatal immunocompetence. Bovine neonates acquire innate and IgM-mediated humoral immunocompetence within first week post-birth.