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*
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201; and
Department of Laboratory Medicine and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510
In the first week of the primary immune response to the
(4-hydroxy-3-nitrophenyl)acetyl (NP) hapten, plasmacytic foci and
germinal centers (GCs) in C57BL/6 mice are comprised of polyclonal
populations of B lymphocytes bearing the 
1 L-chain
(1+). The Ig H-chains of these early populations of B
cells are encoded by a variety of VH and D exons
undiversified by hypermutation while later, oligoclonal populations are
dominated by mutated rearrangements of the VH186.2 and
DFL16.1 gene segments. To assess directly Ab affinities within these
defined splenic microenvironments, representative VDJ rearrangements
were recovered from B cells participating in the early immune response
to NP, inserted into Ig H-chain expression cassettes, and transfected
into J558L (H-; 1+) myeloma cells. These
transfectoma Abs expressed a remarkably wide range of measured
affinities (Ka = 5 x
104-1.3 x 106 M-1) for NP.
VDJs recovered from both foci and early GCs generated comparable
affinities, suggesting that initial differentiation into these
compartments occurs stochastically. We conclude that Ag normally
activates B cells bearing an unexpectedly wide spectrum of Ab
affinities and that this initial, promiscuous clonal activation is
followed by affinity-driven competition to determine survival and
clonal expansion within GCs and entry into the memory and bone marrow
plasmacyte compartments.
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