In contrast to mammals, early B cell differentiation and diversification of the antibody
repertoire in chickens do not take place in the bone marrow but in a specialized gut
associated lymphoid tissue (GALT), the bursa of Fabricius. During embryonic development,
B cell precursors migrate to the bursa anlage, where they proliferate and diversify
their B cell receptor repertoire. Around hatch these diversified B cells start to
emigrate from the bursa of Fabricius and populate peripheral lymphoid organs, but
very little is known how the migratory processes are regulated. As CXCL12 (syn. SDF-1)
and CXCR4 were shown to be essential for the control of B cell migration during the
development of lymphoid tissues in mammals, we analyzed expression and function of
this chemokine/chemokine-receptor pair in the chicken bursa. We found a strong variation
of mRNA abundance of CXCL12 and CXCR4 in different stages of bursa development, with
high abundance of CXCL12 mRNA in the bursa anlage at embryonic day 10 (ED10).In situhybridization
demonstrated disseminated CXCL12 expression in the early bursa anlage, which condensed
in the developing follicles and was mainly restricted to the follicle cortex post-hatch.
Flow cytometric analysis detected CXCR4 protein already on early B cell stages, increasing
during bursal development. Post-hatch, a subpopulation with the hallmarks of emigrating
B cells became detectable, which had lower CXCR4 expression, suggesting that downregulation
of CXCR4 is necessary to leave the CXCL12-high bursal environment.In vivoblockade
of CXCR4 using AMD3100 at the time of B cell precursor immigration strongly inhibited
follicle development, demonstrating that CXCL12 attracts pre-bursal B cells into the
bursal anlage. Altogether, we show that CXCL12 and its receptor CXCR4 are important
for both populating the bursa with B cells and emigration of mature B cells into the
periphery post hatch, and that CXCR4 function in primary B cell organs is conserved
between mammals and birds.
