The newborn has a limited ability to regulate H+/HCO3- homeostasis, du
e in part to immaturity of the intercalated cells in the distal nephro
n. We traced the postnatal differentiation of the intercalated cells o
f the rabbit cortical collecting duct (CCD) and outer medullary collec
ting duct (OMCD) using MAb to the 31-kD subunit of the vacuolar H+-ATP
ase, membrane portion of erythrocyte band 3, and apical surface of B-i
ntercalated cells (peanut agglutinin [PNA], MAb B63). In the most supe
rficial CCD of the newborn there was no binding to these probes, altho
ugh deeper in the cortex there was faint apical staining with PNA and
MAb B63 and a few patterns of H+-ATPase and band 3 labeling of neonata
l intercalated cells. The OMCD showed mostly apical H+-ATPase and both
cytoplasmic and basolateral band 3 labeling but B-intercalated cell m
arkers were not seen. By 3 wk of age the staining of the CCD and OMCD
was more polarized, resembling those in the adult. Band 3 positive cel
ls (as a percentage of total cells) in the CCD increased from 13 to 17
% during maturation, and in the OMCD they increased from 22 to 37%. So
me basolateral band 3 and apical H+-ATPase staining was also seen in t
he inner medullary collecting duct of 3-wk-old rabbits to a greater ex
tent than in newborn or adult rabbits. Labeling of intercalated cells
in the CCD and OMCD was weakest and least numerous in the newborn, gre
ater in the 3 wk old, and greatest in the adult, Most maturing cortica
l intercalated cells bound both PNA and H+-ATPase MAb, comparable to w
hat has been observed in the adult CCD. PNA-negative cells showing api
cal H+-ATPase labeling, consistent with the classic A-intercalated cel
l phenotype, comprised only 5% of identified intercalated cells in the
newborn CCD compared with 12% in older animals. In or near the develo
ping renal vesicles and ampullary structures were occasional cytoplasm
ically staining PNA- and B63-positive cells. Whether these cells are p
recursors of specific renal tubular cells cannot yet be established. S
taining for principal cells (ST.9) was less intense in the neonatal co
rtex than in more mature cortex, but the deep cortex and outer meduIla
were heavily labeled at all ages. These data indicate that immature i
ntercalated cells, in the CCD and OMCD, may undergo significant postna
tal proliferation and differentiation, acquiring mature phenotypes dur
ing the first month of life. The A-intercalated cell appears more diff
erentiated than the B cell during the Ist wk of life, suggesting that
A-intercalated cells contribute more than B cells to the maintenance o
f acid-base homeostasis in the newborn.